Effect of Film Morphology on Electrical Conductivity of PEDOT:PSS.

Commercially available formulations of the popular conductive polymer, poly(3,4-ethylenedioxythiophene):polystyrene sulfonate (PEDOT:PSS) are aqueous dispersions that require the addition of secondary dopants such as dimethyl sulphoxide (DMSO) or ethylene glycol (EG) for fabricated films to have the desired levels of conductivity. CleviosTM F HC Solar, a formulation of PEDOT:PSS produced by Heraeus, GmbH, achieves over 500 S/cm without these secondary dopants. This work studies whether secondary dopants such as DMSO have any additional effect on this type of PEDOT:PSS. The temperature dependencies of the conductivity of F HC Solar spin-coated thin films measured using a four-probe method seem to exhibit different charge transport properties compared with secondary doped PH1000. Observations made using atomic force microscopy (AFM) show that different concentrations of DMSO affect the orientation of the PEDOT domains in the thin film. These morphological changes cause room temperature conductivity to reduce from 640 S/cm in pristine films to as low as 555 S/cm after adding 7 wt% of DMSO along the film. Such tuning may prove useful in future applications of PEDOT:PSS, such as nanoprobes, transistors and hybrid solar cells.

Mechanisms of the antiferro-electric ordering in superprotonic conductors Cs3H(SeO4)2 and Cs3D(SeO4)2.

Wide ranges of absorbance spectra were measured to elucidate a difference in the antiferro-electric (AF) ordering mechanisms below 50 and 168 K in Cs3H(SeO4)2 and Cs3D(SeO4)2, respectively. Collective excitations due to deuterons successfully observed at 610 cm-1 exhibit a remarkable isotope effect. This indicates that the transfer state in the dimer of Cs3D(SeO4)2 is dominated by a deuteron hopping in contrast to Cs3H(SeO4)2, where a proton hopping makes a tiny contribution compared to a phonon-assisted proton tunneling (PAPT) associated with 440-cm-1 defbend . The fluctuation relevant to the AF ordering in Cs3D(SeO4)2 is not driven by the conventional deuteron hopping but by the phonon-assisted deuteron hopping associated with 310-cm-1 defbend . Consequently, Cs3D(SeO4)2 has a distinct ordering mechanism from Cs3H(SeO4)2, in which quantum fluctuations toward the AF ordering are enhanced through the PAPT associated with the in-phase libration.

Erratum: Lattice Dynamics Coupled to Charge and Spin Degrees of Freedom in the Molecular Dimer-Mott Insulator κ-(BEDT-TTF)_{2}Cu[N(CN)_{2}]Cl [Phys. Rev. Lett. 123, 027601 (2019)].

This corrects the article DOI: 10.1103/PhysRevLett.123.027601.

Phonon-assisted proton tunneling in the hydrogen-bonded dimeric selenates of Cs3H(SeO4)2.

In phases III and IV of Cs3H(SeO4)2, the vibrational state and intrabond transfer of the proton in the dimeric selenates are systematically studied with a wide range of absorbance spectra, a spin-lattice relaxation rate of 1H-NMR (T1 -1), and DFT calculations. The OH stretching vibrations have extremely broad absorption at around 2350 (B band) and 3050 cm-1 (A band), which originate from the 0-1 and 0-2 transitions in the asymmetric double minimum potential, respectively. The anharmonic-coupling calculation makes clear that the A band couples not only to the libration but also to the OH bending band. The vibrational state (nano-second order) is observed as the response of the proton basically localized in either of the two equivalent sites. The intrabond transfer between those sites (pico-second order) yields the protonic fluctuation reflected in T1 -1. Together with the anomalous absorption [νp2 phonon, libration, tetrahedral deformation (δ440), and 610-cm-1 band], we have demonstrated that the intrabond transfer above 70 K is dominated by the thermal hopping that is collectively excited at 610 cm-1 and the phonon-assisted proton tunneling (PAPT) relevant to the tetrahedral deformation [PAPT(def)]. Below 70 K, T1 -1 is largely enhanced toward the antiferroelectric ordering and the distinct splitting emerges in the libration, which dynamically modulates the O(2)-O'(2) distance of the dimer. The PAPT(lib) associated with the libration is confirmed to be a driving force of the AF ordering.

Quantum Disordering of an Antiferromagnetic Order by Quenched Randomness in an Organic Mott Insulator.

The behavior of interacting spins subject to randomness is a longstanding issue and the emergence of exotic quantum states is among intriguing theoretical predictions. We show how a quantum-disordered phase emerges from a classical antiferromagnet by controlled randomness. ^{1}H NMR of a successively x-ray-irradiated organic Mott insulator finds that the magnetic order collapses into a spin-glass-like state, immediately after a slight amount of disorder centers are created, and evolves to a gapless quantum-disordered state without spin freezing, spin gap, or critical slowing down, as reported by T. Furukawa et al. [Phys. Rev. Lett. 115, 077001 (2015)]PRLTAO0031-900710.1103/PhysRevLett.115.077001 through sequential reductions in the spin freezing temperature and moment.

Electronic Griffiths Phase in Disordered Mott-Transition Systems.

Solid-state physics and soft-matter physics have been developed independently, with little mutual exchange of the underlying physical concepts. However, after many studies of correlated electron systems, it has been recognized that correlated electrons (especially in Mott-transition systems) in solid matter sometimes show behavior similar to "structured fluids" in soft matter; that is, the electrons exhibit long-length self-organization (but without long-range order) and slow dynamics, which is inevitable for the long-length structures. The essential question is this: what condition causes such behavior in solid matter? We focused on an organic Mott-transition system and demonstrated that the electrons of this system fluctuate very slowly only when the following two factors are met simultaneously: (i) the electronic system is on the metal and Mott-insulator boundary and (ii) the system is subject to quenched disorder. This electronic state with slow dynamics under this condition can be explained by the concept of the "(electronic) Griffiths phase." This concept will potentially be a key in connecting solid-state physics with soft-matter physics.

Lattice Dynamics Coupled to Charge and Spin Degrees of Freedom in the Molecular Dimer-Mott Insulator κ-(BEDT-TTF)_{2}Cu[N(CN)_{2}]Cl.

Inelastic neutron scattering measurements on the molecular dimer-Mott insulator κ-(BEDT-TTF)_{2}Cu[N(CN)_{2}]Cl reveal a phonon anomaly in a wide temperature range. Starting from T_{ins}∼50-60 K where the charge gap opens, the low-lying optical phonon modes become overdamped upon cooling towards the antiferromagnetic ordering temperature T_{N}=27 K, where also a ferroelectric ordering at T_{FE}≈T_{N} occurs. Conversely, the phonon damping becomes small again when spins and charges are ordered below T_{N}, while no change of the lattice symmetry is observed across T_{N} in neutron diffraction measurements. We assign the phonon anomalies to structural fluctuations coupled to charge and spin degrees of freedom in the BEDT-TTF molecules.

Low-Dose Carbon Monoxide Inhibits Rhinovirus Replication in Human Alveolar and Airway Epithelial Cells.

Carbon monoxide (CO) and nitric oxide (NO) exhibit physiological properties that include the activation of guanylate cyclase. NO inhibits replication of rhinovirus (RV), a major cause of the common cold and exacerbation of bronchial asthma and chronic obstructive pulmonary disease. However, the anti-rhinoviral effects of CO remain unclear. This study investigated whether the exogenous application of low-dose CO could inhibit RV replication in human alveolar and airway epithelial cells. A549 human lung carcinoma cells with alveolar epithelial features and primary cultures of human tracheal epithelial (HTE) cells were pretreated with CO (100 ppm) and infected with a major group RV, type 14 RV (RV14). CO exposure reduced RV14 titers in the supernatants and RV RNA levels in A549 and HTE cells. The treatment with a guanylate cyclase inhibitor, 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one, reversed the inhibitory effects of CO exposure on RV14 replication in A549 cells. Pretreatment of A549 cells with 8-Br-cGMP, a cell-permeable cGMP analog, caused the decrease in RV14 replication, while CO exposure increased cGMP production. CO exposure also increased the expression levels of interferon (IFN)-γ mRNA and protein. In contrast, pretreatment with CO did not increase DNA fragmentation and did not reduce the expression of intercellular adhesion molecule-1, the RV14 receptor, or the number of acidic endosomes, through which RV RNA enters the cytoplasm. These findings suggest that low-dose CO may decrease RV14 replication in alveolar and airway epithelial cells. IFN-γ production, which is induced by CO exposure via guanylate cyclase activation-mediated cGMP production, may be involved in RV14 replication inhibition.

Breakdown of Hooke's law of elasticity at the Mott critical endpoint in an organic conductor.

The Mott metal-insulator transition, a paradigm of strong electron-electron correlations, has been considered as a source of intriguing phenomena. Despite its importance for a wide range of materials, fundamental aspects of the transition, such as its universal properties, are still under debate. We report detailed measurements of relative length changes ΔL/L as a function of continuously controlled helium-gas pressure P for the organic conductor κ-(BEDT-TTF)2Cu[N(CN)2]Cl across the pressure-induced Mott transition. We observe strongly nonlinear variations of ΔL/L with pressure around the Mott critical endpoint, highlighting a breakdown of Hooke's law of elasticity. We assign these nonlinear strain-stress relations to an intimate, nonperturbative coupling of the critical electronic system to the lattice degrees of freedom. Our results are fully consistent with mean-field criticality, predicted for electrons in a compressible lattice with finite shear moduli. We argue that the Mott transition for all systems that are amenable to pressure tuning shows the universal properties of an isostructural solid-solid transition.

KdmB, a Jumonji Histone H3 Demethylase, Regulates Genome-Wide H3K4 Trimethylation and Is Required for Normal Induction of Secondary Metabolism in Aspergillus nidulans.

Histone posttranslational modifications (HPTMs) are involved in chromatin-based regulation of fungal secondary metabolite biosynthesis (SMB) in which the corresponding genes-usually physically linked in co-regulated clusters-are silenced under optimal physiological conditions (nutrient-rich) but are activated when nutrients are limiting. The exact molecular mechanisms by which HPTMs influence silencing and activation, however, are still to be better understood. Here we show by a combined approach of quantitative mass spectrometry (LC-MS/MS), genome-wide chromatin immunoprecipitation (ChIP-seq) and transcriptional network analysis (RNA-seq) that the core regions of silent A. nidulans SM clusters generally carry low levels of all tested chromatin modifications and that heterochromatic marks flank most of these SM clusters. During secondary metabolism, histone marks typically associated with transcriptional activity such as H3 trimethylated at lysine-4 (H3K4me3) are established in some, but not all gene clusters even upon full activation. KdmB, a Jarid1-family histone H3 lysine demethylase predicted to comprise a BRIGHT domain, a zinc-finger and two PHD domains in addition to the catalytic Jumonji domain, targets and demethylates H3K4me3 in vivo and mediates transcriptional downregulation. Deletion of kdmB leads to increased transcription of about ~1750 genes across nutrient-rich (primary metabolism) and nutrient-limiting (secondary metabolism) conditions. Unexpectedly, an equally high number of genes exhibited reduced expression in the kdmB deletion strain and notably, this group was significantly enriched for genes with known or predicted functions in secondary metabolite biosynthesis. Taken together, this study extends our general knowledge about multi-domain KDM5 histone demethylases and provides new details on the chromatin-level regulation of fungal secondary metabolite production.

Histone H1 Limits DNA Methylation in Neurospora crassa.

Histone H1 variants, known as linker histones, are essential chromatin components in higher eukaryotes, yet compared to the core histones relatively little is known about their in vivo functions. The filamentous fungus Neurospora crassa encodes a single H1 protein that is not essential for viability. To investigate the role of N. crassa H1, we constructed a functional FLAG-tagged H1 fusion protein and performed genomic and molecular analyses. Cell fractionation experiments showed that H1-3XFLAG is a chromatin binding protein. Chromatin-immunoprecipitation combined with sequencing (ChIP-seq) revealed that H1-3XFLAG is globally enriched throughout the genome with a subtle preference for promoters of expressed genes. In mammals, the stoichiometry of H1 impacts nucleosome repeat length. To determine if H1 impacts nucleosome occupancy or nucleosome positioning in N. crassa, we performed micrococcal nuclease digestion in the wild-type and the [Formula: see text]hH1 strain followed by sequencing (MNase-seq). Deletion of hH1 did not significantly impact nucleosome positioning or nucleosome occupancy. Analysis of DNA methylation by whole-genome bisulfite sequencing (MethylC-seq) revealed a modest but global increase in DNA methylation in the [Formula: see text]hH1 mutant. Together, these data suggest that H1 acts as a nonspecific chromatin binding protein that can limit accessibility of the DNA methylation machinery in N. crassa.

Genome-wide redistribution of H3K27me3 is linked to genotoxic stress and defective growth.

H3K9 methylation directs heterochromatin formation by recruiting multiple heterochromatin protein 1 (HP1)-containing complexes that deacetylate histones and methylate cytosine bases in DNA. In Neurospora crassa, a single H3K9 methyltransferase complex, called the DIM-5,-7,-9, CUL4, DDB1 Complex (DCDC), is required for normal growth and development. DCDC-deficient mutants are hypersensitive to the genotoxic agent methyl methanesulfonate (MMS), but the molecular basis of genotoxic stress is unclear. We found that both the MMS sensitivity and growth phenotypes of DCDC-deficient strains are suppressed by mutation of embryonic ectoderm development or Su-(var)3-9; E(z); Trithorax (set)-7, encoding components of the H3K27 methyltransferase Polycomb repressive complex-2 (PRC2). Trimethylated histone H3K27 (H3K27me3) undergoes genome-wide redistribution to constitutive heterochromatin in DCDC- or HP1-deficient mutants, and introduction of an H3K27 missense mutation is sufficient to rescue phenotypes of DCDC-deficient strains. Accumulation of H3K27me3 in heterochromatin does not compensate for silencing; rather, strains deficient for both DCDC and PRC2 exhibit synthetic sensitivity to the topoisomerase I inhibitor Camptothecin and accumulate γH2A at heterochromatin. Together, these data suggest that PRC2 modulates the response to genotoxic stress.

Critical slowing down of the charge carrier dynamics at the Mott metal-insulator transition.

We report on the dramatic slowing down of the charge carrier dynamics in a quasi-two-dimensional organic conductor, which can be reversibly tuned through the Mott metal-insulator transition (MIT). At the finite-temperature critical end point, we observe a divergent increase of the resistance fluctuations accompanied by a drastic shift of spectral weight to low frequencies, demonstrating the critical slowing down of the order parameter (doublon density) fluctuations. The slow dynamics is accompanied by non-Gaussian fluctuations, indicative of correlated charge carrier dynamics. A possible explanation is a glassy freezing of the electronic system as a precursor of the Mott MIT.

Methylated DNA is over-represented in whole-genome bisulfite sequencing data.

The development of whole-genome bisulfite sequencing (WGBS) has resulted in a number of exciting discoveries about the role of DNA methylation leading to a plethora of novel testable hypotheses. Methods for constructing sodium bisulfite-converted and amplified libraries have recently advanced to the point that the bottleneck for experiments that use WGBS has shifted to data analysis and interpretation. Here we present empirical evidence for an over-representation of reads from methylated DNA in WGBS. This enrichment for methylated DNA is exacerbated by higher cycles of PCR and is influenced by the type of uracil-insensitive DNA polymerase used for amplifying the sequencing library. Future efforts to computationally correct for this enrichment bias will be essential to increasing the accuracy of determining methylation levels for individual cytosines. It is especially critical for studies that seek to accurately quantify DNA methylation levels in populations that may segregate for allelic DNA methylation states.

Optical freezing of charge motion in an organic conductor.

Dynamical localization, that is, reduction of the intersite electronic transfer integral t by an alternating electric field, E(ω), is a promising strategy for controlling strongly correlated systems with a competing energy balance between t and the Coulomb repulsion energy. Here we describe a charge localization induced by the 9.3 MV cm(-1) instantaneous electric field of a 1.5 cycle (7 fs) infrared pulse in an organic conductor α-(bis[ethylenedithio]-tetrathiafulvalene)(2)I(3). A large reflectivity change of >25% and a coherent charge oscillation along the time axis reflect the opening of the charge ordering gap in the metallic phase. This optical freezing of charges, which is the reverse of the photoinduced melting of electronic orders, is attributed to the ~10% reduction of t driven by the strong, high-frequency (ω ≧ t/h) electric field.

Heterochromatin controls γH2A localization in Neurospora crassa.

In response to genotoxic stress, ATR and ATM kinases phosphorylate H2A in fungi and H2AX in animals on a C-terminal serine. The resulting modified histone, called γH2A, recruits chromatin-binding proteins that stabilize stalled replication forks or promote DNA double-strand-break repair. To identify genomic loci that might be prone to replication fork stalling or DNA breakage in Neurospora crassa, we performed chromatin immunoprecipitation (ChIP) of γH2A followed by next-generation sequencing (ChIP-seq). γH2A-containing nucleosomes are enriched in Neurospora heterochromatin domains. These domains are comprised of A·T-rich repetitive DNA sequences associated with histone H3 methylated at lysine-9 (H3K9me), the H3K9me-binding protein heterochromatin protein 1 (HP1), and DNA cytosine methylation. H3K9 methylation, catalyzed by DIM-5, is required for normal γH2A localization. In contrast, γH2A is not required for H3K9 methylation or DNA methylation. Normal γH2A localization also depends on HP1 and a histone deacetylase, HDA-1, but is independent of the DNA methyltransferase DIM-2. γH2A is globally induced in dim-5 mutants under normal growth conditions, suggesting that the DNA damage response is activated in these mutants in the absence of exogenous DNA damage. Together, these data suggest that heterochromatin formation is essential for normal DNA replication or repair.

Optical conductivity measurement of a dimer Mott-insulator to charge-order phase transition in a two-dimensional quarter-filled organic salt compound.

We report a novel insulator-insulator transition arising from the internal charge degrees of freedom in the two-dimensional quarter-filled organic salt ß-(meso-DMBEDT-TTF)2PF6. The optical conductivity spectra above Tc=70 K display a prominent feature of the dimer Mott insulator, characterized by a substantial growth of a dimer peak near 0.6 eV with decreasing temperature. The dimer peak growth is rapidly quenched as soon as a peak of the charge order appears below Tc, indicating a competition between the two insulating phases. Our infrared imaging spectroscopy has further revealed a spatially competitive electronic phase far below Tc, suggesting a nature of quantum phase transition driven by material-parameter variations.

Levofloxacin inhibits rhinovirus infection in primary cultures of human tracheal epithelial cells.

Respiratory virus infections, including infections with rhinoviruses (RVs), are related to exacerbations of chronic obstructive pulmonary disease (COPD). A new quinolone antibiotic, levofloxacin (LVFX), has been used to treat bacterial infections that cause COPD exacerbations as well as bacterial infections that are secondary to viral infection in COPD patients. However, the inhibitory effects of LVFX on RV infection and RV infection-induced airway inflammation have not been studied. We examined the effects of LVFX on type 14 rhinovirus (RV14) (a major human RV) infection of human tracheal epithelial cells pretreated with LVFX. LVFX pretreatment reduced the RV14 titer, the level of cytokines in the supernatant, the amount of RV14 RNA in the cells after RV14 infection, and the cells' susceptibility to RV14 infection. LVFX pretreatment decreased the mRNA level of intercellular adhesion molecule 1 (ICAM-1), a receptor for RV14, in the cells and the concentration of the soluble form of ICAM-1 in the supernatant before RV14 infection. LVFX pretreatment also decreased the number and the fluorescence intensity of the acidic endosomes from which RV14 RNA enters the cytoplasm. LVFX pretreatment inhibited the activation of nuclear factor κB proteins, including p50 and p65, in nuclear extracts. LVFX pretreatment did not reduce the titers of RV2 (a minor human RV) but reduced the titers of RV15 (a major human RV). These results suggest that LVFX inhibits major-group rhinovirus infections in part by reducing ICAM-1 expression levels and the number of acidic endosomes. LVFX may also modulate airway inflammation in rhinoviral infections.

Nitric oxide (NO) enhances pemetrexed cytotoxicity via NO­cGMP signaling in lung adenocarcinoma cells in vitro and in vivo.

Pemetrexed (PEM) is a novel, multitargeted, antifolate, antineoplastic agent for the treatment of non-small cell lung cancer and malignant pleural mesothelioma. Additional effects of nitric oxide (NO) donors on the chemosensitivity of cancers have been reported. However, the effects of an NO donor on PEM-induced cytotoxicity remain unknown. In this study, we investigated the effects of the NO donors, NOC-18 on the cytotoxicity in A549 cells in vitro and of nitroglycerin (GTN), on the tumor growth of Lewis lung carcinoma cells in a murine syngraft model treated with PEM. The effects of NO donors on the expression of proteins associated with PEM metabolism, including thymidylate synthase (TS), reduced folate carrier 1 (RFC1), folylpolyglutamate synthase (FPGS), γ-glutamyl hydrolase (GGH) and multidrug resistance-related protein (MRP)5, and the effects of cyclic guanosine mono-phosphate (cGMP) signaling on these proteins were examined in A549 cells. Treatment with 100 nM NOC-18 for 3 days significantly enhanced PEM-induced cytotoxicity and increased the expression of RFC1 and FPGS in A549 cells. Treatment with 10 nM 8-bromo-cGMP (8-Br-cGMP) for 3 days also increased the expression of RFC1 and FPGS in A549 cells. 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) (10 µm) significantly reversed the increase in RFC1 and FPGS expression induced by 100 nM NOC-18 in A549 cells. Combination therapy with GTN and PEM significantly reduced tumor growth compared with PEM alone in the syngraft model. The enhanced antitumor effect of GTN plus PEM was significantly reversed by the concomitant addition of ODQ. These findings suggest that NO donors, such as NOC-18 and GTN, enhance the anticancer effects of PEM by increasing the RFC1 and FPGS expression and stimulating cGMP signaling pathways in cancer cells.

Inhibitory effects of tiotropium on rhinovirus infection in human airway epithelial cells.

Infection by rhinoviruses (RVs) causes exacerbations of chronic obstructive pulmonary disease (COPD). The long-acting anti-cholinergic agent tiotropium reduces the frequency of COPD exacerbations, but the inhibitory effects of tiotropium on the COPD exacerbations induced by RVs are unclear. Likewise, the effects of tiotropium on RVs infection remain to be studied. To examine the effects of tiotropium on RV infection and RV infection-induced airway inflammation, human tracheal epithelial cells were infected with a major group RV, type 14 RV (RV14). RV14 infection increased the viral titre and the amount of pro-inflammatory cytokines, including interleukin (IL)-1ß and -6, in supernatant fluids and the amount of RV14 RNA in cells. Tiotropium reduced RV14 titres, RNA and cytokine concentrations, and susceptibility to RV14 infection. Tiotropium reduced the expression of intercellular adhesion molecule (ICAM)-1, the receptor for RV14, and the number of cellular acidic endosomes, which allow RV14 RNA to enter the cytoplasm. Tiotropium inhibited the activation of nuclear factor-(κ)B proteins, including p50 and p65, in the nuclear extracts, and it increased the cytosolic amount of inhibitory κB-α. Tiotropium may inhibit RV14 infection by reducing the levels of ICAM-1 and acidic endosomes and may also modulate airway inflammation in rhinovirus infection.