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A 57-year-old woman presented with a 20-year history of progressive lower extremity weakness, spasticity, and proprioception deficits. She was given a diagnosis of primary progressive multiple sclerosis at age 38. Her Achilles tendons were enlarged (figure 1). Brain MRI was normal. Spine MRI demonstrated T2-hyperintense signal involving the posterior and lateral columns (figure 2). Serum cholestanol level was elevated. CYP27A1 gene sequencing revealed 2 pathogenic variants, c.1183C>T(p.Arg395Cys) and c.410G>A(p.Arg137Gln), confirming the diagnosis of cerebrotendinous xanthomatosis (CTX). Spinal xanthomatosis is a rare variant of CTX presenting with progressive corticospinal and posterior column signs.1 Early treatment with chenodeoxycholic acid may improve outcomes.2

The end-capping group (EG) is the essential electron-withdrawing component of nonfullerene acceptors (NFAs) in bulk heterojunction (BHJ) organic solar cells (OSCs). To systematically probe the impact of two frequent EG functionalization strategies, π-extension and halogenation, in A-DAD-A type NFAs, we synthesized and characterized four such NFAs: BT-BIC, LIC, L4F, and BO-L4F. To assess the relative importance of these strategies, we contrast these NFAs with the baseline acceptors, Y5 and Y6. Up to 16.6% power conversion efficiency (PCE) in binary inverted OSCs with BT-BO-L4F combining π-extension and halogenation was achieved. When these two factors are combined, the effect on optical absorption is cumulative. Single-crystal π-π stacking distances are similar for the EG strategies of π-extension. Increasing the alkyl substituent length from BT-L4F to BT-BO-L4F significantly alters the packing motif and eliminates the EG core interactions of BT-L4F. Electronic structure computations reveal some of the largest NFA π-π electronic couplings observed to date, 103.8 meV in BT-L4F and 47.5 meV in BT-BO-L4F. Computed electronic reorganization energies, 132 and 133 meV for BT-L4F and BT-BO-L4F, respectively, are also lower than Y6 (150 meV). BHJ blends show preferential π-face-on orientation, and both fluorination and π-extension increase NFA crystallinity. Femto/nanosecond transient absorption spectroscopy (fs/nsTA) and integrated photocurrent device analysis (IPDA) indicate that π-extension modifies the phase separation to enhance film ordering and carrier mobility, while fluorination suppresses unimolecular recombination. This systematic study highlights the synergistic effects of NFA π-extension and fluorination in affording efficient OSCs and provides insights into designing next-generation materials.

Emerging nonfullerene acceptors (NFAs) with crystalline domains enable high-performance bulk heterojunction (BHJ) solar cells. Thermal annealing is known to enhance the BHJ photoactive layer morphology and performance. However, the microscopic mechanism of annealing-induced performance enhancement is poorly understood in emerging NFAs, especially regarding competing factors. Here, optimized thermal annealing of model system PBDB-TF:Y6 (Y6 = 2,2'-((2Z,2'Z)-((12,13-bis(2-ethylhexyl)-3,9-diundecyl-12,13-dihydro-[1,2,5]thiadiazolo[3,4-e]thieno[2″,3'':4',5']thieno[2',3':4,5]pyrrolo[3,2-g]thieno[2',3':4,5]-thieno[3,2-b]indole-2,10-diyl)bis(methanylylidene))bis(5,6-difluoro-3-oxo-2,3-dihydro-1H-indene-2,1-diylidene))dimalononitrile) decreases the open circuit voltage (VOC) but increases the short circuit current (JSC) and fill factor (FF) such that the resulting power conversion efficiency (PCE) increases from 14 to 15% in the ambient environment. Here we systematically investigate these thermal annealing effects through in-depth characterizations of carrier mobility, film morphology, charge photogeneration, and recombination using SCLC, GIXRD, AFM, XPS, NEXAFS, R-SoXS, TEM, STEM, fs/ns TA spectroscopy, 2DES, and impedance spectroscopy. Surprisingly, thermal annealing does not alter the film crystallinity, R-SoXS characteristic size scale, relative average phase purity, or TEM-imaged phase separation but rather facilitates Y6 migration to the BHJ film top surface, changes the PBDB-TF/Y6 vertical phase separation and intermixing, and reduces the bottom surface roughness. While these morphology changes increase bimolecular recombination (BR) and lower the free charge (FC) yield, they also increase the average electron and hole mobility by at least 2-fold. Importantly, the increased μh dominates and underlies the increased FF and PCE. Single-crystal X-ray diffraction reveals that Y6 molecules cofacially pack via their end groups/cores, with the shortest π-π distance as close as 3.34 A, clarifying out-of-plane π-face-on molecular orientation in the nanocrystalline BHJ domains. DFT analysis of Y6 crystals reveals hole/electron reorganization energies of as low as 160/150 meV, large intermolecular electronic coupling integrals of 12.1-37.9 meV rationalizing the 3D electron transport, and relatively high μe of 10-4 cm2 V-1 s-1. Taken together, this work clarifies the richness of thermal annealing effects in high-efficiency NFA solar cells and tasks for future materials design.

Here we report facile, high-yield synthetic access to the difluoro BTA building block, 4,7-bis(5-bromo-4-(2-hexyl-decyl)-thiophen-2-yl)-5,6-difluoro-2-(pentadecan-7-yl)-benzo[d]thiazole (BTAT-2f), ...

The assessment of the degree to which biological communities in streams impaired by acid mine drainage (AMD) are restored by passive treatment has focused primarily on eukaryotic-cell organisms and microbial processes. The responses of microbial community structure to passive treatment have received much less attention, even though functional processes such as nutrient cycling and organic matter decomposition depend on taxonomic composition. Our objective was to determine the degree to which passive treatment restored microbial communities in three types of habitats: aqueous, leaf, and sediment. To assess their recovery, we compared the community composition in these habitats based on 16S rRNA gene sequencing at three different stream sites: an untreated AMD site (U), a remediated site below AMD passive treatment (T), and an unimpaired reference site (R). The acidity, conductivity, and soluble metal concentrations at T were found to be elevated compared to R, but generally 1–2 orders of magnitude less than at U. Microbial community composition was found to be synergistically affected by habitat type and AMD impact, with the similarity among communities in the three habitats increasing with the severity of the AMD. Sediment- and leaf-associated microbial communities at U were characterized by taxa that are tolerant to severe AMD. The absence of the nitrogen oxidizing bacterium Nitrospira in sediment communities at T and U was found to correspond to higher NH4+ concentrations compared to R, possibly because of the presence of iron oxyhydroxide precipitate. In contrast, the microbial composition was found to be similar between the T and R sites for both aqueous and leaf communities, indicating that passive treatment was more able to restore these communities to the reference condition than sediment communities. The remediation of AMD streams should consider the habitat-specific responses of microbial community composition and be guided by future studies that empirically couple changes in taxonomic composition to measured functional processes.

Study of the double detonation Type Ia supernova scenario, in which a helium shell detonation triggers a carbon core detonation in a sub-Chandrasekhar-mass white dwarf, has experienced a resurgence in the past decade. New evolutionary scenarios and a better understanding of which nuclear reactions are essential have allowed for successful explosions in white dwarfs with much thinner helium shells than in the original, decades-old incarnation of the double detonation scenario. In this paper, we present the first suite of light curves and spectra from multi-dimensional radiative transfer calculations of thin-shell double detonation models, exploring a range of white dwarf and helium shell masses. We find broad agreement with the observed light curves and spectra of non-peculiar Type Ia supernovae, from subluminous to overluminous subtypes, providing evidence that double detonations of sub-Chandrasekhar-mass white dwarfs produce the bulk of observed Type Ia supernovae. Some discrepancies in spectral velocities and colors persist, but these may be brought into agreement by future calculations that include more accurate initial conditions and radiation transport physics., Accepted for publication in ApJ. Same as previous arXiv version

Achieving efficient polymer solar cells (PSCs) requires a structurally optimal donor-acceptor heterojunction morphology. Here we report the combined experimental and theoretical characterization of a benzodithiophene-benzothiadiazole donor polymer series (PBTZF4-R; R = alkyl substituent) blended with the non-fullerene acceptor ITIC-Th, and analyse the effects of substituent dimensions on blend morphology, charge transport, carrier dynamics, and PSC metrics. Varying substituent dimensions has a pronounced effect on the blend morphology with a direct link between domain purity, to some extent domain dimensions, and charge generation and collection. The polymer with the smallest alkyl substituent yields the highest PSC power conversion efficiency (PCE, 11%), reflecting relatively small, high-purity domains, and possibly benefiting from “matched” donor polymer - small molecule acceptor orientations. The distinctive morphologies arising from the substituents are investigated using molecular dynamics (MD) computation which reveals that substituent dimensions dictate a well-defined set of polymer conformations, in turn driving chain aggregation, and ultimately, the various film morphologies and mixing with acceptor small molecules. A straightforward energetic parameter explains the experimental polymer domain morphological trends, hence PCE, and suggests strategies for substituent selection to optimize PSC materials morphologies.

Due to the highly directional nature of transport in polymer-based organic field-effect transistors (OFETs), alignment of the polymer backbone can significantly affect device performance. While man...

Developing earth abundant catalysts for clean energy technologies is vital to address the issues related to the use of fossil fuels and associated pollution, which adversely affects human health. H...

Chemical-looping dry (CO2) reforming (CLDR) of CH4 over the LaxCe1-x-Fe2O3/Al2O3 (x = 0, 0.33, 0.67, and 1) redox catalysts paves a novel path for efficient syngas production and intensive CO2 reduction. The isolation of CO2 splitting (CS) from partial oxidation of CH4 (POM) via the proposed CLDR process makes it possible to economically address the carbon deposition of significant concern in conventional dry reforming and other related applications, and meanwhile enable a straightforward determination of active phases involved in the cyclic CLDR operation. Owing to the rare earth (i.e., La and Ce) incorporations and intimate contacts among the active Fe species, a large amount of perovskite (LaFeO3 and CeFeO3)-derived oxygen defects along with CeO2-assisted surface dispersion improvement hammer out tunnels beneficial for lattice oxygen migration, hence constituting the synergistic La-Ce effect. Moreover, our findings reveal that such La-Ce effect is advantageous for enhancing the resistance of Fe2O3/Al2O3 redox catalyst toward particle sintering and formation of inactive carbon, which guarantees catalyst tolerance against accumulated carbon deposition and more importantly the effective CO2 activation for both lattice oxygen replenishment and carbon removal. Herein, our findings demonstrate the potential of utilizing LaxCe1-x-Fe2O3/Al2O3 (x = 0.33) as a most promising redox catalyst for the proposed CLDR process.

Myelin oligodendrocyte glycoprotein (MOG)-IgG-associated optic neuritis has been established as a new entity of optic neuropathy. We will review recent advances in pathophysiology, diagnosis, and clinical manifestations of MOG-IgG-associated optic neuritis to better understand its distinctive characteristics.MOG is expressed on the surface of myelin sheaths and oligodendrocytes. MOG is highly immunogenic and is a potential target of inflammatory demyelinating disease. MOG-IgG activate immune responses and cause demyelination without astrocytopathy. MOG-IgG are measured by cell-based assays, which have higher sensitivity and specificity than ELISA. Patients with MOG-IgG-associated optic neuritis present with initially severe vision loss, are more likely to have optic disc edema, but have favorable visual outcomes. Furthermore, patients with MOG-IgG-associated optic neuritis have higher rates of recurrence compared with MOG-IgG seronegative patients. MOG-IgG-associated optic neuritis responds well to steroid treatment, however, close monitoring for signs of relapse and long-term immunosuppression may be necessary.MOG-IgG associated optic neuritis demonstrates distinctive pathophysiological and clinical characteristics from optic neuritis in aquaporin4-IgG seropositive or multiple sclerosis patients. Measurements of MOG-IgG titers by cell-based assays will be helpful for the diagnosis and treatment of optic neuritis.

Polymer chains are attached to nanoparticle surfaces for many purposes, including altering solubility, influencing aggregation, dispersion, and even tailoring immune responses in drug delivery. The most unique structural motif of polymer-grafted nanoparticles (PGNs) is the high-density region in the corona where polymer chains are stretched under significant confinement, but orientation of these chains has never been measured because conventional nanoscale-resolved measurements lack sensitivity to polymer orientation in amorphous regions. Here, we directly measure local chain orientation in polystyrene grafted gold nanoparticles using polarized resonant soft X-ray scattering (P-RSoXS). Using a computational scattering pattern simulation approach, we measure the thickness of the anisotropic region of the corona and extent of chain orientation within it. These results demonstrate the power of P-RSoXS to discover and quantify orientational aspects of structure in amorphous soft materials and provide a framework for applying this emerging technique to more complex, chemically heterogeneous systems in the future., The orientation of polymer chains in the corona of polymer-grafted nanoparticles has never been measured. Here, the authors use polarized resonant soft X-ray scattering to measure local chain orientation in polystyrene grafted gold nanoparticles and quantify the thickness of the anisotropic region of the corona as well as the extent of chain orientation within it.

The ancient stress signaling molecule abscisic acid (ABA) is ubiquitous in animals and plants but is perhaps most well-known from its early discovery as a plant hormone. ABA can be released into water by plants and is found in nectar, but is also present in mammalian blood, three key contexts for mosquito biology. We previously established that addition of ABA to Anopheles stephensi larval rearing water altered immature development and life history traits of females derived from treated larvae, while addition of ABA to an infected bloodmeal increased resistance of adult female A. stephensi to human malaria parasite infection. Here we sought to determine whether larval treatment with ABA could similarly impact resistance to parasite infection in females derived from treated larvae and, if so, whether resistance could be extended to another parasite species. We examined nutrient levels and gene expression to demonstrate that ABA can transstadially alter resistance to a rodent malaria parasite with hallmarks of previously observed mechanisms of resistance following provision of ABA in blood to A. stephensi.

Background Myelin oligodendrocyte glycoprotein-immunoglobulin G (MOG-IgG) associated disorder (MOGAD) is a CNS demyelinating disease distinct from neuromyelitis optica spectrum disorder (NMOSD) and multiple sclerosis. Some patients with MOGAD exhibit a highly-relapsing and steroid-dependent disease course for which optimal treatment is unknown. Interleukin-6 (IL-6) plays an important pathobiologic role in NMOSD with aquaporin-4 antibodies and preliminary data suggest similar mechanisms of CNS damage may occur in MOGAD. Objective To summarize our experience with and all current literature on the use of tocilizumab, an IL-6 inhibitor, for highly-relapsing MOGAD along with the underlying immunopathologic rationale. Methods This is a single-center report from a U.S. military tertiary referral hospital of all patients with clinically, radiographically, and serologically confirmed MOGAD who were treated with tocilizumab compiled with data from five other case series/reports from tertiary referral centers. The main outcomes of interest were reduction in annualized relapse rate and required dose of oral prednisone for symptomatic management. Results Ten total patients with relapsing MOGAD who were treated with intravenous or subcutaneous tocilizumab were identified. At our institution, a 20 year-old female with a 9-year history of highly-relapsing and steroid dependent MOGAD was treated with tocilizumab. In 28 months of follow up, she had no clinical relapses and was able to discontinue corticosteroids. Another 35 year-old female at our institution with a 10-year history of highly-relapsing and steroid dependent MOGAD was treated with tocilizumab for 6 months. Tocilizumab therapy was associated with relapse freedom, resolution of eye pain, and ability to discontinue corticosteroids. When compiled with data from all other case reports of relapsing MOGAD treated with tocilizumab, there have been zero clinical or radiographic relapses in 10 patients over an average treatment duration of 28.6 months. Conclusions Tocilizumab is an IL-6 inhibitor that may be a promising therapeutic option for patients with relapsing MOGAD that has not responded to other immunotherapies. Our results support a key role for IL-6-related mechanisms in MOGAD disease activity. Its safety and tolerability profile, both in our own experience and based on its use for other FDA approved conditions, may even justify its use a first line therapy in select patients. Further research is needed to establish the safety and efficacy of IL-6 inhibition in MOGAD.

Highlights • The role of pre-existing immunosuppression on COVID-19 risk and outcomes is unclear • Immunotherapy is being evaluated for COVID-19-related cytokine release syndrome • We report a fingolimod-treated MS patient who developed severe COVID-19 • COVID-19 recovery occurred after stopping fingolimod and treating with tocilizumab, Background : Treatment decisions in patients with multiple sclerosis (MS) during the coronavirus disease 2019 (COVID-19) pandemic are challenging. It is not known whether and how various disease modifying therapies, especially immunosuppressive drugs, affect COVID-19 risk and disease course. Methods : Case report Results : We report a fingolimod-treated MS patient who developed severe COVID-19 but recovered after treatment with tocilizumab. Conclusion : This report suggests that a brief course of tocilizumab for the treatment of severe COVID-19 may be effective while not aggravating pre-existing MS.

From 2001&ndash, 2018, a series of fuel reduction and ecosystem restoration treatments were implemented in the southern Appalachian Mountains near Asheville, North Carolina, USA. Treatments consisted of prescribed fire (four burns), mechanical cutting of understory shrubs and mid-story trees (two cuttings), and a combination of both cutting and prescribed fire (two cuts + four burns). Soils were sampled in 2018 to determine potential treatment impacts for O horizon and mineral soil (0&ndash, 10 cm depth) carbon (C) and nitrogen (N) and mineral soil calcium (Ca), magnesium (Mg), phosphorus (P), potassium (K), and pH. Results suggested that mean changes in O horizon C and N and mineral soil C, N, C:N, Ca, and P from 2001&ndash, 2018 differed between the treatments, but only mineral soil C, N, C:N and Ca displayed differences between at least one fuel reduction treatment and the untreated control. One soils-related restoration objective was mineral soil N reduction and the cut + burn treatment best achieved this result. Increased organic matter recalcitrance was another priority, but this was not obtained with any treatment. When paired with previously reported fuels and vegetation results from this site, it appeared that continued use of the cut + burn treatment may best achieve long-term management objectives for this site and other locations being managed for similar long-term restoration and fuels management objectives.

The larval environment of holometabolous insects determines many adult life history traits including, but not limited to, rate and success of development and adult lifespan and fecundity. The ancient stress signaling hormone abscisic acid (ABA), released by plants inundated with water and by leaf and root fragments in water, is likely ubiquitous in the mosquito larval environment and is well known for its wide ranging effects on invertebrate biology. Accordingly, ABA is a relevant stimulus and signal for mosquito development. In our studies, the addition of ABA at biologically relevant levels to larval rearing containers accelerated the time to pupation and increased death of A. stephensi pupae. We could not attribute these effects, however, to ABA-dependent changes in JH biosynthesis-associated gene expression, 20E titers or transcript patterns of insulin-like peptide genes. Adult females derived from ABA-treated larvae had reduced total protein content and significantly reduced post blood meal transcript expression of vitellogenin, effects that were consistent with variably reduced egg clutch sizes and oviposition success from the first through the third gonotrophic cycles. Adult female A. stephensi derived from ABA-treated larvae also exhibited reduced lifespans relative to controls. Collectively, these effects of ABA on A. stephensi life history traits are robust, durable and predictive of multiple impacts of an important malaria vector spreading to new malaria endemic regions.

Author(s): Augustine, CN; Willcox, DE; Brooks, J; Townsley, DM; Calder, AC | Abstract: The creation of "hybrid" white dwarfs, made of a C-O core within an O-Ne shell has been proposed, and studies indicate that ignition in the C-rich central region makes these viable progenitors for thermonuclear (type Ia) supernovae. Recent work found that the C-O core is mixed with the surrounding O-Ne as the white dwarf cools prior to accretion, which results in lower central C fractions in the massive progenitor than previously assumed. To further investigate the efficacy of hybrid white dwarfs as progenitors of thermonuclear supernovae, we performed simulations of thermonuclear supernovae from a new series of hybrid progenitors that include the effects of mixing during cooling. The progenitor white dwarf model was constructed with the one-dimensional stellar evolution code Modules for Experiments in Stellar Astrophysics (MESA) and represented a star evolved through the phase of unstable interior mixing followed by accretion until it reached conditions for the ignition of carbon burning. This MESA model was then mapped to a two-dimensional initial condition for explosions simulated with FLASH. For comparison, similar simulations were performed for a traditional C-O progenitor white dwarf. By comparing the yields of the explosions, we find that, as with earlier studies, the lower C abundance in the hybrid progenitor compared to the traditional C-O progenitor leads to a lower average yield of 56Ni. Although the unmixed hybrid white dwarf showed a similar decrement also in total iron-group yield, the mixed case does not and produces a smaller fraction of iron-group elements in the form of 56Ni. We attribute this to the higher central density required for ignition and the location, center or off-center, of deflagration ignition.

Photocatalysts formed from a single organic semiconductor typically suffer from inefficient intrinsic charge generation, which leads to low photocatalytic activities. We demonstrate that incorporating a heterojunction between a donor polymer (PTB7-Th) and non-fullerene acceptor (EH-IDTBR) in organic nanoparticles (NPs) can result in hydrogen evolution photocatalysts with greatly enhanced photocatalytic activity. Control of the nanomorphology of these NPs was achieved by varying the stabilizing surfactant employed during NP fabrication, converting it from a core–shell structure to an intermixed donor/acceptor blend and increasing H2 evolution by an order of magnitude. The resulting photocatalysts display an unprecedentedly high H2 evolution rate of over 60,000 µmol h−1 g−1 under 350 to 800 nm illumination, and external quantum efficiencies over 6% in the region of maximum solar photon flux. Photocatalysts formed from a single organic semiconductor can suffer from inefficient charge generation leading to low photocatalytic activities. Incorporating a heterojunction between a donor polymer and non-fullerene acceptor in organic nanoparticles leads to enhanced photocatalytic hydrogen evolution.

Surface catalytic interconversion of hydroquinone (H2Q) and 1,4-benzoquinone (Q) occur at a fluorine-doped tin oxide electrode (FTO) modified by the addition of the surface-bound couple, [Os(bpy)2((4,4′-PO3H2)2bpy)]3+/2+ (OsP2+, bpy = bipyridine and 4,4′-(PO3H2)2 = 4,4′-phosphonato-2,2′-bipyridine). Significant rate enhancements are observed with the added solution buffers—phosphate, acetate, and citrate—and a surface-bound, pyridine base. Analysis of cyclic voltammograms for the 2e–/2H+ couple, by use of the Butler–Volmer equation, point to the importance of acid–base effects and H-bonding in enhancing the reaction rate at the electrode.

Acid mine drainage environments have multiple stressors, making it difficult to isolate effects of individual contaminants on benthic algal communities in situ in order to develop more specific indicators. Additionally, responses to AMD contaminants may be dependent on the abiotic and biotic conditions within the affected stream. We examined the efficacy of using chemical diffusing substrata (CDS) to determine how acid and metals interact to affect benthic algae in 2 streams with different trophy. CDS containing Mn, Fe, Al, acid, Mn + acid, Fe + acid, and Al + acid were deployed in a flow-through system to determine flux from the liquid media. Flux values for metals ranged from 1.0 to 18.1 µg/cm2/d for 5 days, and 0.5–7.4 µg/cm2/d for 21 days. Flux values for H+ were 467 (5 day) and 212 (21 day) µg/cm2/d. Corresponding water column concentrations that would produce the same flux as CDS metal treatments were estimated to be in the low to mid toxicity range for Al, low range for Fe, and nontoxic range for Mn. Acid treatments were estimated to be equivalent to a stream pH of 2.1–2.5. Five replicates of each CDS treatment, and a water control, were placed into a high-alkalinity, eutrophic stream (Wolf Creek) for 5 days and a low-alkalinity, oligotrophic stream (Silver Creek) for 21 days, respectively. In Silver Creek, all treatments except circumneutral Fe and circumneutral Mn had significantly lower algal cell densities than control treatments. Cell densities were significantly lower on Al + acid and Mn + acid than on the acid-only treatment, indicating synergistic effects. Cell densities were not significantly different among treatments in Wolf Creek. Higher alkalinity, nutrients, and productivity in this stream likely increased neutralization and detoxification processes within the biofilm. However, significantly lower chlorophyll a and higher phaeophytin concentrations of communities on treatments containing acid indicated sublethal effects. Significantly more acid tolerant taxa occurred on treatments with acid in Silver Creek, and significantly more metal-tolerant taxa occurred on metal treatments in Wolf Creek. However, treatment effects on taxonomic composition appeared to be constrained by the species pool within each stream, as these indicator taxa made up less than 4% of any community. Although equating CDS flux of contaminants to water column concentrations requires assumptions, and flux decreases over the exposure period, this study indicates that in situ experiments using CDS can separate out effects of individual toxic components on benthic algae, and determine context-dependent responses.

The morphological, structural, and electrical properties of poly(3-methylthiophene) polymer brush films grown on indium tin oxide up to 120 nm thick are reported. Optical spectroscopy experiments indicate that the average orientation of polymer chains is nearly isotropic at thicknesses below 10 nm and above 30 nm, and exhibits mild vertical anisotropy in between. Atomic force microscopy shows that the film surfaces consist of column-shaped domains with an average cross-sectional area (2.3 × 10–3 μm2) and density (200 μm–2) that are independent of film thickness. Analysis of the contact between printed Au electrodes and the polymer brush film shows that a small fraction of the film surface (i.e., the tallest columns) makes contact with the electrodes. The measured bulk resistivity along the columns is 1.4 × 105 Ω·cm, 2 orders of magnitude lower than typical values for spuncast poly(3-alkylthiophene) films, while the resistance along individual polymer chains in the columns is estimated to be 360 GΩ/nm per ...

Although increasing evidence indicates that endothelin-2 (Edn2) has distinct roles in tissue pathology, including inflammation, glial cell dysfunction, and angiogenesis, its role in the retina and the factors that regulate its actions are not fully understood. We hypothesized that Edn2 damages the blood–retinal barrier (BRB) and that this is mediated by interactions with the renin–angiotensin–aldosterone system and reactive oxygen species derived from NADPH oxidase (Nox). C57BL/6J mice received an intravitreal injection of Edn2 or control vehicle to examine the blood pressure–independent effects of Edn2. Mice administered Edn2 were randomized to receive by intraperitoneal injection treatments that inhibited the Edn type a receptor, Edn type b receptor, angiotensin type 1 receptor, mineralocorticoid receptor, or Nox isoforms 1 to 4. One month later, mice administered Edn2 exhibited breakdown of the BRB with increased vascular leakage, vascular endothelial growth factor expression, and infiltrating macrophages (Ly6C + CD45 high CD11b + ). Further, macroglial Muller cells, which influence the integrity of the BRB and prevent retinal edema, became gliotic and expressed increased levels of water (aquaporin-4) and ion (Kir4.1) channels. This Edn2-mediated retinopathy was reduced by all treatments. Complementary in vitro studies in cultured Muller cells supported these findings and demonstrated the importance of reactive oxygen species in mediating these events. In conclusion, Edn2 has detrimental effects on the BRB and Muller cells that involve interactions with the renin-angiotensin aldosterone system and Nox1/4.

Recent demonstration of mobilities in excess of 10 cm2 V–1 s–1 have energized research in solution deposition of polymers for thin film transistor applications. Due to the lamella motif of most soluble, semiconducting polymers, the local mobility is intrinsically anisotropic. Therefore, fabrication of aligned films is of interest for optimization of device performance. Many techniques have been developed to control film alignment, including solution deposition via directed flows and deposition on topologically structured substrates. We report device and detailed structural analysis (ultraviolet–visible absorption, IR absorption, near-edge X-ray absorption (NEXAFS), grazing incidence X-ray diffraction, and atomic force microscopy) results from blade coating two high performing semiconducting polymers on unpatterned and nanostructured substrates. Blade coating exhibits two distinct operational regimes: the Landau–Levich or horizontal dip coating regime and the evaporative regime. We find that in the evapora...

Syntheses of new asymmetric pincer precursors 1,3-C6H4{CH2P(tBu,X)}2 (tBu,XPCPH; X = Cl, SiMe3, OPh) and a new class of hybrid donor/acceptor pincer ligands 1,3-C6H4{CH2P(tBu,Rf)}2 (tBu,RfPCPH; Rf = CF3, C2F5) are reported. All tBu,XPCPH compounds are obtained as mixtures of meso and rac diastereomers in varying ratios (meso : rac ∼ 4 : 1 to 3 : 2) which were used without separation. Treatment of Ru(cot)(cod) with tBu,CF3PCPH under 1 atm H2 in acetone at 20 °C produced the hydride solvate (tBu,CF3PCP)Ru(acetone)xH which was not isolated, but could be trapped as stable diene complexes (tBu,CF3PCP)Ru(L)2H (L2 = cod (), nbd ()). Catalytic cyclooctane dehydrogenation studies demonstrate that has ∼50% the activity of (CF3PCP)Ru(cod)(H), but significantly higher catalyst stability and is able to operate at higher catalyst loading concentrations without deactivation via bimolecular decomposition.

Despite the importance of Type Ia supernovae (SNe Ia) throughout astronomy, the precise progenitor systems and explosion mechanisms that drive SNe Ia are still unknown. An explosion scenario that has gained traction recently is the double detonation in which an accreted shell of He detonates and triggers a secondary detonation in the underlying white dwarf. Our research presents a number of high resolution, multi-dimensional, full star simulations of thin-He-shell, sub-Chandrasekhar-mass white dwarf progenitors that undergo a double detonation. This suite of thin-shell progenitors incorporates He shells that are thinner than those in previous multi-dimensional studies. We confirm the viability of the double detonation across a range of He shell parameter space as well as present bulk yields and ejecta profiles for each progenitor. The yields obtained are generally consistent with previous works and indicate the likelihood of producing observables that resemble SNe Ia. The dimensionality of our simulations allow us to examine features of the double detonation more closely, including the details of the off-center secondary ignition and asymmetric ejecta. We find considerable differences in the high-velocity extent of post-detonation products across different lines of sight. The data from this work will be used to generate predicted observables and may further support the viability of the double detonation scenario as a SNe Ia channel as well as show how properties of the progenitor or viewing angle may influence trends in observable characteristics., 20 pages, 9 figures, 11 tables, accepted for publication in ApJ

Transition state search is at the center of multiple types of computational chemical predictions related to mechanistic investigations, reactivity and regioselectivity predictions, and catalyst design. The process of finding transition states in practice is, however, a laborious multistep operation that requires significant user involvement. Here, we report a highly automated workflow designed to locate transition states for a given elementary reaction with minimal setup overhead. The only essential inputs required from the user are the structures of the separated reactants and products. The seamless workflow combining computational technologies from the fields of cheminformatics, molecular mechanics, and quantum chemistry automatically finds the most probable correspondence between the atoms in the reactants and the products, generates a transition state guess, launches a transition state search through a combined approach involving the relaxing string method and the quadratic synchronous transit, and finally validates the transition state via the analysis of the reactive chemical bonds and imaginary vibrational frequencies as well as by the intrinsic reaction coordinate method. Our approach does not target any specific reaction type, nor does it depend on training data; instead, it is meant to be of general applicability for a wide variety of reaction types. The workflow is highly flexible, permitting modifications such as a choice of accuracy, level of theory, basis set, or solvation treatment. Successfully located transition states can be used for setting up transition state guesses in related reactions, saving computational time and increasing the probability of success. The utility and performance of the method are demonstrated in applications to transition state searches in reactions typical for organic chemistry, medicinal chemistry, and homogeneous catalysis research. In particular, applications of our code to Michael additions, hydrogen abstractions, Diels-Alder cycloadditions, carbene insertions, and an enzyme reaction model involving a molybdenum complex are shown and discussed.

A major goal of the Convert Program of the U.S. Department of Energy's National Nuclear Security Administration (DOE/NNSA) is to enable high-performance research reactors to operate with low-enriched uranium rather than the high-enriched uranium currently used. To this end, uranium alloyed with 10 wt% molybdenum (U-10Mo) represents an ideal candidate because of its stable gamma phase, low neutron caption cross section, acceptable swelling response, and predictable irradiation behavior. However, because of the complexities of the fuel design and the need for rolled monolithic U-10Mo foils, new developments in processing and fabrication are necessary. This study used a finite-element code, LS-DYNA, as a predictive tool to optimize the rolling process. Simulations of the hot rolling of U-10Mo coupons encapsulated in low-carbon steel were conducted following two different schedules. Model predictions of the roll-separation force and roll pack thicknesses at different stages of the rolling process were compared with experimental measurements. The study reported here discussed various attributes of the rolled coupons revealed by the model (e.g., waviness and thickness non-uniformity like dog-boning). To investigate the influence of the cladding material on these rolling defects, other cases were simulated: hot rolling with alternative can materials, namely, 304 stainless steel and Zircaloy-2, and bare-rolling. Simulation results demonstrated that reducing the mismatch in strength between the coupon and can material improves the quality of the rolled sheet. Bare-rolling simulation results showed a defect-free rolled coupon. The finite-element model developed and presented in this study can be used to conduct parametric studies of several process parameters (e.g., rolling speed, roll diameter, can material, and reduction).

Solution-processed organic films are a facile route to high-speed, low cost, large-area deposition of electrically functional components (transistors, solar cells, emitters, etc.) that can enable a diversity of emerging technologies, from Industry 4.0, to the Internet of things, to point-of-use heath care and elder care. The extreme sensitivity of the functional performance of organic films to structure and the general nonequilibrium nature of solution drying result in extreme processing-performance correlations. In this Review, we highlight insights into the fundamentals of solution-based film deposition afforded by recent state-of-the-art in situ measurements of functional film drying. Emphasis is placed on multimodal studies that combine surface-sensitive X-ray scattering (GIWAXS or GISAXS) with optical characterization to clearly define the evolution of solute structure (aggregation, crystallinity, and morphology) with film thickness.

The evolution of the morphology of a high-efficiency, blade-coated, organic-photovoltaic (OPV) active layer containing the low band gap polymer poly[(4,8-bis[5-(2-ethylhexyl)thiophene-2-yl]benzo[1,2-b:4,5-b′]dithiophene)-2,6-diyl-alt-(4-(2-ethylhexanoyl)-thieno[3,4-b]thiophene))-2,6-diyl] (PBDTTT-C-T) is examined by in situ X-ray scattering. In situ studies enable real-time characterization of the effect of the processing additive 1,8-diiodoocatane (DIO) on the active layer morphology. In the presence of DIO, X-ray scattering indicates that domain structure radically changes and increases in purity, while X-ray diffraction reveals little change in crystallinity/local order. The solidification behavior of this active layer differs dramatically from those that strongly crystallize such as poly(3-hexylthiophene) and small molecule containing systems, exposing significant diversity in the solidification routes relevant to high-efficiency polymer–fullerene OPV processing. In the presence of DIO, we find quanti...

Naphthenic acids (NAs), a class of structurally diverse carboxylic acids with often complex ring structures and large aliphatic tail groups, are important by-products of many petrochemical processes including the oil sands mining activity of Northern Alberta. While it is evident that NAs have both acute and chronic harmful effects on many organisms, many aspects of their toxicity remain to be clarified. Particularly, while substantive data sets have been collected on NA toxicity in aquatic prokaryote and vertebrate model systems, to date, nothing is known about the toxic effects of these compounds on the embryonic development of aquatic invertebrate taxa, including freshwater mollusks. This study examines under laboratory conditions the toxicity of NAs extracted from oil sands process water (OSPW) and the low-molecular weight model NAs cyclohexylsuccinic acid (CHSA), cyclohexanebutyric acid (CHBA), and 4-tert-butylcyclohexane carboxylic acid (4-TBCA) on embryonic development of the snail Lymnaea stagnalis, a common freshwater gastropod with a broad Palearctic distribution. Evidence is provided for concentration-dependent teratogenic effects of both OSPW-derived and model NAs with remarkably similar nominal threshold concentrations between 15 and 20 mg/L and 28d EC50 of 31 mg/L. In addition, the data provide evidence for substantial toxicokinetic differences between CHSA, CHBA and 4-TBCA. Together, our study introduces Lymnaea stagnalis embryonic development as an effective model to assay NA-toxicity and identifies molecular architecture as a potentially important toxicokinetic parameter in the toxicity of low-molecular weight NA in embryonic development of aquatic gastropods.

We consider the conformational flexibility of molecules and its implications for micro- and macro-pKa. The corresponding formulas are derived and discussed against the background of a comprehensive scientific and algorithmic description of the latest version of our computer program Jaguar pKa, a density functional theory-based pKa predictor, which is now capable of acting on multiple conformations explicitly. Jaguar pKa is essentially a complex computational workflow incorporating research and technologies from the fields of cheminformatics, molecular mechanics, quantum mechanics, and implicit solvation models. The workflow also makes use of automatically applied empirical corrections which account for the systematic errors resulting from the neglect of explicit solvent interactions in the algorithm’s implicit solvent model. Applications of our program to large, flexible organic molecules representing several classes of functional groups are shown, with a particular emphasis in illustrations laid on drug-...