The DNA dioxygenase Tet1 regulates H3K27 modification and embryonic stem cell biology independent of its catalytic activity.

Tet enzymes (Tet1/2/3) oxidize 5-methylcytosine to promote DNA demethylation and partner with chromatin modifiers to regulate gene expression. Tet1 is highly expressed in embryonic stem cells (ESCs), but its enzymatic and non-enzymatic roles in gene regulation are not dissected. We have generated Tet1 catalytically inactive (Tet1m/m) and knockout (Tet1-/-) ESCs and mice to study these functions. Loss of Tet1, but not loss of its catalytic activity, caused aberrant upregulation of bivalent (H3K4me3+; H3K27me3+) developmental genes, leading to defects in differentiation. Wild-type and catalytic-mutant Tet1 occupied similar genomic loci which overlapped with H3K27 tri-methyltransferase PRC2 and the deacetylase complex Sin3a at promoters of bivalent genes and with the helicase Chd4 at active genes. Loss of Tet1, but not loss of its catalytic activity, impaired enrichment of PRC2 and Sin3a at bivalent promoters leading to reduced H3K27 trimethylation and deacetylation, respectively, in absence of any changes in DNA methylation. Tet1-/-, but not Tet1m/m, embryos expressed higher levels of Gata6 and were developmentally delayed. Thus, the critical functions of Tet1 in ESCs and early development are mediated through its non-catalytic roles in regulating H3K27 modifications to silence developmental genes, and are more important than its catalytic functions in DNA demethylation.

Cannabis Use and the Onset of Cigarette and E-cigarette Use: A Prospective, Longitudinal Study Among Youth in the United States.

INTRODUCTION: Cigarette use is declining among youth in the United States, whereas cannabis use and e-cigarette use are increasing. Cannabis use has been linked with increased uptake and persistence of cigarette smoking among adults. The goal of this study was to examine whether cannabis use is associated with the prevalence and incidence of cigarette, e-cigarette, and dual product use among U.S. youth. METHODS: Data included U.S. youth ages 12-17 from two waves of the Population Assessment of Tobacco and Health (PATH) Study (Wave 1 youth, n = 13 651; Wave 1 tobacco-naive youth, n = 10 081). Weighted logistic regression models were used to examine the association between Wave 1 cannabis use and (1) Wave 1 prevalence of cigarette/e-cigarette use among Wave 1 youth and (2) Wave 2 incidence of cigarette/e-cigarette use among Wave 1 tobacco-naive youth. Analyses were run unadjusted and adjusted for demographics and internalizing/externalizing problem symptoms. RESULTS: Wave 1 cigarette and e-cigarette use were significantly more common among youth who used versus did not use cannabis. Among Wave 1 tobacco-naive youth, Wave 1 cannabis use was associated with significantly increased incidence of cigarette and e-cigarette use by Wave 2. CONCLUSIONS: Youth who use cannabis are more likely to report cigarette and e-cigarette use, and cannabis use is associated with increased risk of initiation of cigarette and e-cigarette use over 1 year. Continued success in tobacco control-specifically toward reducing smoking among adolescents-may require focusing on cannabis, e-cigarette, and cigarette use in public health education, outreach, and intervention efforts. IMPLICATIONS: These data extend our knowledge of cigarette and e-cigarette use among youth by showing that cannabis use is associated with increased prevalence and incidence of cigarette and e-cigarette use among youth, relative to youth who do not use cannabis. The increasing popularity of cannabis use among youth and diminished perceptions of risk, coupled with the strong link between cannabis use and tobacco use, may have unintended consequences for cigarette control efforts among youth.

Synthesis of gold nanostructures using glycine as the reducing agent.

Biological synthesis of gold nanostructures could potentially offer an environmentally friendly alternative to traditional chemical synthetic methods. During the last decades, various biomolecules, including amino acids, have been successfully used as reducing and capping agents to synthesize multi-shaped gold nanostructures. A grand challenge in this field is to increase our ability to control the size and shape of gold nanostructures formed precisely by systematic synthetic approaches based on the understanding of the mechanism for structural determination. In this study, using glycine as the model amino acid and chloroaurate (AuCl4 -) ions as the precursor solution, we report the finding that the shape of the gold nanostructures synthesized showed a strong correlation with the speciation of gold complexes determined by the pH, precursor concentration and chloride concentration of the solvent system. The gold chloro-hydroxy speciation [AuClx(OH)4-x]- (with x = 0-4) influenced the shape of the gold nanostructures formed, with gold nanoplatelets, nanotriangles, nanokites and nanoribbons observed at x = 4, 3, 2 and 1, respectively, and spherical nanoparticles observed at x = 0. Glycine was found to play a role as a reducing agent, but no significant effect on the morphology was observed, indicating the dominance of gold chloro-hydroxy speciation in the structural formation. These results collectively provide synthetic considerations to systematically synthesize non-spherical to spherical biosynthesized gold nanostructures by controlling the speciation of [AuClx(OH)4-x]-.

Trends in Cigar Use in the United States, 2002-2016: Diverging Trends by Race/Ethnicity.

INTRODUCTION: Although there are racial/ethnic differences in cigarette use, little is known about how non-cigarette tobacco use differs among racial/ethnic groups. This study investigated trends in cigar use from 2002 to 2016, by racial/ethnic group, in nationally representative US data. METHODS: Data were drawn from the 2002-2016 National Survey on Drug Use and Health public use data files (total analytic sample n = 630 547 including 54 060 past-month cigar users). Linear time trends of past-month cigar use were examined by racial/ethnic group (Non-Hispanic [NH] White, NH Black, Hispanic, NH Other/Mixed Race/Ethnicity) using logistic regression models. RESULTS: In 2016, the prevalence of past-month cigar use was significantly higher among NH Black respondents than among other racial/ethnic groups (ps < .001). Cigar use was also higher among NH White respondents than among Hispanic and NH Other/Mixed Race/Ethnicity respondents. The year by racial/ethnic group interaction was significant (p < .001). Past-month cigar use decreased significantly from 2002 to 2016 among NH White and Hispanic respondents (ps = .001), whereas no change in prevalence was observed among NH Black (p = .779) and NH Other/Mixed Race/Ethnicity respondents (p = .152). Cigar use decreased for NH White men (p < .001) and did not change for NH White women (p = .884). Conversely, cigar use increased for NH Black women (p < .001) and did not change for NH Black men (p = .546). CONCLUSIONS: Cigar use remains significantly more common among NH Black individuals in the United States and is not declining among NH Black and NH Other/Mixed Race/Ethnicity individuals over time, in contrast to declines among NH White and Hispanic individuals. IMPLICATIONS: This study identified racial/ethnic differences in trends in past-month cigar use over 15 years among annual cross-sectional samples of US individuals. The highest prevalence of cigar use in 2016 was found among NH Black individuals. In addition, cigar use prevalence did not decline from 2002 to 2016 among NH Black and NH Other/Mixed Race/Ethnicity groups over time, in contrast to NH White and Hispanic groups. Further, cigar use increased over time for NH Black women. Targeted public health and clinical efforts may be needed to decrease the prevalence of cigar use, especially for NH Black individuals.

Cannabis Use Is Associated With Increased Risk of Cigarette Smoking Initiation, Persistence, and Relapse Among Adults in the United States.

INTRODUCTION: Despite increasing use of cannabis, it is unclear how cannabis use is related to cigarette transitions. This study examined cannabis use and smoking initiation, persistence, and relapse over 1 year among a nationally representative sample of US adults. METHODS: Data were from US adults (≥18 years) who completed two waves of longitudinal data from the Population Assessment of Tobacco and Health Study (Wave 1, 2013-2014; Wave 2, 2014-2015; n = 26 341). Logistic regression models were used to calculate the risk of Wave 2 incident smoking among Wave 1 never-smokers, smoking cessation among Wave 1 smokers, and smoking relapse among Wave 1 former smokers by Wave 1 cannabis use. Analyses were adjusted for age, gender, race/ethnicity, income, and education. RESULTS: Among Wave 1 never-smokers, cannabis use was associated with increased odds of initiation of nondaily (adjusted odds ratio [AOR] = 5.50, 95% confidence limits [CL] = 4.02-7.55) and daily cigarette smoking (AOR = 6.70, 95% CL = 4.75-9.46) 1 year later. Among Wave 1 daily smokers, cannabis use was associated with reduced odds of smoking cessation (AOR = 0.36, 95% CL = 0.20-0.65). Among Wave 1 former smokers, cannabis use was associated with increased odds of relapse to daily and nondaily cigarette smoking (daily AOR = 1.90, 95% CL = 1.11-3.26; nondaily AOR = 2.33, 95% CL = 1.61-3.39). CONCLUSIONS: Cannabis use was associated with increased cigarette smoking initiation, decreased smoking cessation, and increased smoking relapse among adults in the United States. Increased public education about the relationship between cannabis use and cigarette smoking transitions may be needed as cannabis use becomes more common among US adults. IMPLICATIONS: As cannabis use increases in the United States and other countries, an evaluation of the relationships of cannabis use to other health-related behaviors (eg, cigarette smoking) is needed to understand the population-level impact of legalization. Little is known about associations between cannabis use and cigarette smoking transitions (1) using recent longitudinal data, (2) among adults, and (3) examining transitions other than smoking initiation (eg, smoking relapse). Our results suggest that among US adults, cannabis use was associated with increased cigarette smoking initiation among never-smokers, decreased cigarette smoking cessation among current smokers, and increased cigarette smoking relapse among former smokers.

Cigarette smoking quit ratios among adults in the USA with cannabis use and cannabis use disorders, 2002-2016.

BACKGROUND: The prevalence of cigarette smoking is nearly three times higher among persons who use cannabis and have cannabis use disorders (CUDs), relative to those who do not. The current study examined cigarette quit ratios from 2002 to 2016 among US adults with and without cannabis use and CUDs. METHODS: The current study analysed US adults aged 18 years and older from the National Survey on Drug Use and Health, an annual cross-sectional study. Quit ratios (ie, proportion of former smokers among ever-smokers) were calculated annually from 2002 to 2016. Time trends in quit ratios by cannabis use/CUDs were tested using logistic regression. RESULTS: In 2016, the quit ratios for people with any cannabis use (23%) and CUDs (15%) were less than half the quit ratios of those without cannabis use and CUDs (51% and 48%, respectively). After controlling for demographics and substance use disorders, the quit ratio did not change from 2002 to 2016 among persons with CUD, though it non-linearly increased among persons with cannabis use, without cannabis use and without CUDs. Quit ratios increased more rapidly among those who reported past-month cannabis use compared with those without past-month cannabis use. CONCLUSIONS: Cigarette smoking quit ratios remain dramatically lower among people who use cannabis and have CUDs and quit ratios did not change significantly from 2002 to 2016 among those with CUDs. Public health and clinical attention are needed to increase quit ratios and reduce harmful cigarette smoking consequences for persons with cannabis use and CUDs.

Dual-reporter SERS-based biomolecular assay with reduced false-positive signals.

We present a sensitive and quantitative protein detection assay that can efficiently distinguish between specific and nonspecific target binding. Our technique combines dual affinity reagents with surface-enhanced Raman spectroscopy (SERS) and chemometric analysis. We link one Raman reporter-tagged affinity reagent to gold nanoparticles and another to a gold film, such that protein-binding events create a "hot spot" with strong SERS spectra from both Raman reporter molecules. Any signal generated in this context is indicative of recognition by both affinity labels, whereas signals generated by nonspecific binding lack one or the other label, enabling us to efficiently distinguish true from false positives. We show that the number of hot spots per unit area of our substrate offers a quantitative measure of analyte concentration and demonstrate that this dual-label, SERS-linked aptasensor assay can sensitively and selectively detect human α-thrombin in 1% human serum with a limit of detection of 86 pM.

Highly enhanced voltage holding property for low-frequency-driven fringe-field switching liquid crystal mode by charge-trapping effect of carbon-nanotube-doped surface.

We herein propose a multiwalled carbon nanotube (MWCNT) doping method into liquid crystal (LC) alignment polyimides (PIs) with low resistivity for resolving both issues of voltage holding and image sticking in low-frequency-driven fringe-field switching (FFS) LC modes using negative dielectric LCs (n-LCs). By utilizing strong ion trapping ability of MWCNTs, the FFS n-LC cell aligned by low resistivity PIs with 0.05 wt% MWCNT doping exhibited an excellent voltage holding ratio of 99% under an extremely low operation frequency of 0.5 Hz and approximately 23.6 times better surface discharging property than that aligned by high resistivity PIs.

Racial/ethnic differences in daily, nondaily, and menthol cigarette use and smoking quit ratios in the United States: 2002 to 2016.

In the United States (US), racial/ethnic groups differ in cigarette smoking behaviors. We examined changes in cigarette prevalence and quit ratios over 15 years by racial/ethnic group (Non-Hispanic (NH) White, NH Black, Hispanic, NH Other). Data were drawn from the 2002-2016 National Survey on Drug Use and Health (NSDUH) public use data files and analyzed in 2018. Linear time trends of the prevalence of daily, nondaily, and menthol cigarette use and quit ratios (i.e., proportion of former smokers among lifetime smokers) were assessed using logistic regression models. 19.35% of NH White persons were daily smokers in 2016; this prevalence was significantly higher than all other groups (NH Black 10.99%, Hispanic 6.81%, NH Other 9.10%). Menthol use was significantly more common among NH Black individuals than all other groups in every year from 2002 to 2016 (2016: NH Black 23.38%, NH White 14.52%, Hispanic 10.49%, NH Other 8.97%). From 2002 to 2016, daily and nondaily smoking decreased significantly among all groups. The rate of decline of nondaily smoking was more rapid among Hispanic than NH White individuals while the rate of menthol smoking decline was more rapid among NH White than among Hispanic individuals. The quit ratio did not change significantly from 2002 to 2016 among NH Black individuals (31% to 35%) in contrast to a significant increase among NH White (2002, 45%; 2016, 50%) and Hispanic (2002, 33%; 2016, 41%) individuals. Further progress in tobacco control for vulnerable groups may need to include innovative strategies to address these concerning trends.

Fast-switching optically isotropic liquid crystal nano-droplets with improved depolarization and Kerr effect by doping high k nanoparticles.

We proposed and analyzed an optically isotropic nano-droplet liquid crystal (LC) doped with high k nanoparticles (NPs), exhibiting enhanced Kerr effects, which could be operated with reduced driving voltages. For enhancing the contrast ratio together with the light efficiencies, the LC droplet sizes were adjusted to be shorter than the wavelength of visible light to reduce depolarization effects by optical scattering of the LC droplets. Based on the optical analysis of the depolarization effects, the influence of the relationship between the LC droplet size and the NP doping ratio on the Kerr effect change was investigated.

Panchromatic photoproduction of H2 with surface plasmons.

The optical resonances of plasmonic nanostructures depend critically on the geometrical details of the absorber. We show that this unique property of plasmons can potentially be used to create panchromatic absorbers covering most of the useful solar spectrum, by measuring the light-to-hydrogen conversion capabilities of a series multielectrode photocatalytic devices, based on functionalized gold nanorods of appropriately chosen aspect ratios. Judiciously combining nanorods of various aspect ratios almost doubles the H2 production of the device over what is optimally possible with a device using gold nanorods of a single aspect ratio (all other key parameters being equal). The estimated quantum efficiency (absorbed photons-to-hydrogen) averaged over the entire solar spectrum of the best performing plasmonic multielectrode array was approximately 0.1%, and the measured H2 production rate for all of the devices was found to be approximately proportional to the hot electron generation. The device was monitored continuously for over 200 hr of operation without measurable diminution in the rate.

Transient flickering behavior in fringe-field switching liquid crystal mode analyzed by positional asymmetric flexoelectric dynamics.

We analyzed a transient blinking phenomenon in a fringe-field switching liquid crystal (LC) mode that occurred at the moment of frame change even in the optimized DC offset condition for minimum image flicker. Based on the positional dynamic behaviors of LCs by using a high-speed camera, we found that the transient blink is highly related to the asymmetric responses of the splay-bend transitions caused by the flexoelectric (FE) effect. To remove the transient blink, the elastic property adjustment of LCs was an effective solution because the FE switching dynamics between the splay-enhanced and bend-enhanced deformations are highly dependent on the elastic constants of LCs, which is the cause of momentary brightness drop.

A high transmittance color liquid crystal display mode with controllable color gamut and transparency.

In this paper, we propose a color transparent liquid crystal (LC) mode that can control the properties of the color gamut and transparency in a single panel. To achieve high transmittance in the transparent LC mode, a reactive mesogen (RM) with embedded color dichroic dyes was applied instead of a color filter. Basically, the LC mode applied a 3-terminal electrode structure to switch between the transparent LC mode and the conventional color LC mode. Depending on the direction of the applied voltage, we can operate both the color mode and the transparent mode in a single panel, and modulate the transparency and color purity of the cell through appropriate voltage control. In the experiments, we confirmed that the transmittance and the color gamut of the cell were 39.4% and 2% in the transparent LC mode and 14.9% and 34% in the color LC mode, respectively. Modulation of the color gamut and transparency between each LC mode are also demonstrated in the paper.

Synthesis of chemicals using solar energy with stable photoelectrochemically active heterostructures.

Efficient and cost-effective conversion of solar energy to useful chemicals and fuels could lead to a significant reduction in fossil hydrocarbon use. Artificial systems that use solar energy to produce chemicals have been reported for more than a century. However the most efficient devices demonstrated, based on traditionally fabricated compound semiconductors, have extremely short working lifetimes due to photocorrosion by the electrolyte. Here we report a stable, scalable design and molecular level fabrication strategy to create photoelectrochemically active heterostructure (PAH) units consisting of an efficient semiconductor light absorber in contact with oxidation and reduction electrocatalysts and otherwise protected by alumina. The functional heterostructures are fabricated by layer-by-layer, template-directed, electrochemical synthesis in porous anodic aluminum oxide membranes to produce high density arrays of electronically autonomous, nanostructured, corrosion resistant, photoactive units (~10(9)-10(10) PAHs per cm(2)). Each PAH unit is isolated from its neighbor by the transparent electrically insulating oxide cellular enclosure that makes the overall assembly fault tolerant. When illuminated with visible light, the free floating devices have been demonstrated to produce hydrogen at a stable rate for over 24 h in corrosive hydroiodic acid electrolyte with light as the only input. The quantum efficiency (averaged over the solar spectrum) for absorbed photons-to-hydrogen conversion was 7.4% and solar-to-hydrogen energy efficiency of incident light was 0.9%. The fabrication approach is scalable for commercial manufacturing and readily adaptable to a variety of earth abundant semiconductors which might otherwise be unstable as photoelectrocatalysts.

Plasmonic photoanodes for solar water splitting with visible light.

We report a plasmonic water splitting cell in which 95% of the effective charge carriers derive from surface plasmon decay to hot electrons, as evidenced by fuel production efficiencies up to 20-fold higher at visible, as compared to UV, wavelengths. The cell functions by illuminating a dense array of aligned gold nanorods capped with TiO(2), forming a Schottky metal/semiconductor interface which collects and conducts the hot electrons to an unilluminated platinum counter-electrode where hydrogen gas evolves. The resultant positive charges in the Au nanorods function as holes and are extracted by an oxidation catalyst which electrocatalytically oxidizes water to oxygen gas.

Plasmonic photosensitization of a wide band gap semiconductor: converting plasmons to charge carriers.

A fruitful paradigm in the development of low-cost and efficient photovoltaics is to dope or otherwise photosensitize wide band gap semiconductors in order to improve their light harvesting ability for light with sub-band-gap photon energies.(1-8) Here, we report significant photosensitization of TiO2 due to the direct injection by quantum tunneling of hot electrons produced in the decay of localized surface-plasmon polaritons excited in gold nanoparticles (AuNPs) embedded in the semiconductor (TiO2). Surface plasmon decay produces electron-hole pairs in the gold.(9-15) We propose that a significant fraction of these electrons tunnel into the semiconductor's conduction band resulting in a significant electron current in the TiO2 even when the device is illuminated with light with photon energies well below the semiconductor's band gap. Devices fabricated with (nonpercolating) multilayers of AuNPs in a TiO2 film produced over 1000-fold increase in photoconductance when illuminated at 600 nm over what TiO2 films devoid of AuNPs produced. The overall current resulting from illumination with visible light is ∼50% of the device current measured with UV (ℏω>Eg band gap) illumination. The above observations suggest that plasmonic nanostructures (which can be fabricated with absorption properties that cover the full solar spectrum) can function as a viable alternative to organic photosensitizers for photovoltaic and photodetection applications.

Tet-mediated DNA demethylation regulates specification of hematopoietic stem and progenitor cells during mammalian embryogenesis.

Ten-eleven translocation (Tet) enzymes promote DNA demethylation by oxidizing 5-methylcytosine. They are expressed during development and are essential for mouse gastrulation. However, their postgastrulation functions are not well established. We find that global or endothelial-specific loss of all three Tet enzymes immediately after gastrulation leads to reduced number of hematopoietic stem and progenitor cells (HSPCs) and lethality in mid-gestation mouse embryos. This is due to defects in specification of HSPCs from endothelial cells (ECs) that compromise primitive and definitive hematopoiesis. Mechanistically, loss of Tet enzymes in ECs led to hypermethylation and down-regulation of NFκB1 and master hematopoietic transcription factors (Gata1/2, Runx1, and Gfi1b). Restoring Tet catalytic activity or overexpression of these factors in Tet-deficient ECs rescued hematopoiesis defects. This establishes Tet enzymes as activators of hematopoiesis programs in ECs for specification of HSPCs during embryogenesis, which is distinct from their roles in adult hematopoiesis, with implications in deriving HSPCs from pluripotent cells.

Fast switching of long-pitch cholesteric liquid crystal device.

We propose a long-pitch cholesteric liquid crystal (ChLC) device capable of operation in both the dynamic mode and the memory mode. Fast switching between the homeotropic state and the focal conic state allows the display of moving pictures at a low operating voltage. In addition, we can write text messages on the proposed ChLC device by applying an external pressure locally to switch it from the focal conic state to the planar state.

High performance transflective liquid crystal display associated with fringe-field switching device.

The outdoor readability of the most popular portable liquid crystal display (LCDs) viz. fringe field switching has been addressed both in single and dual cell gap transflective devices. The devices use dual orientation, such as, homogeneous alignment in transmissive (T) part and 64° twisted alignment in reflective (R) part. The dark states of the proposed devices are achieved by controlling phase retardation in T part and polarization rotation in R part and the white state is realized by rotating optic axis of liquid crystal and removing phase retardation in T and R parts, respectively. The devices show high light efficiency without requiring any optical compensation films, exhibiting strong potential for portable display applications.

Long-pitch cholesteric liquid crystal cell for switchable achromatic reflection.

We propose a switchable achromatic reflector using a long-pitch cholesteric liquid crystal (CLC) whose Bragg reflection wavelength is chosen to be infrared by controlling the pitch of the CLC so that the planar texture is transparent over the entire visible wavelength. By using the light scattering of the focal conic texture, achromatic reflection can be achieved. Both textures are stable at zero electric field and the operating voltage of the proposed CLC device is much lower than that of conventional CLC devices. The proposed switchable reflector, which can be operated at a low voltage with low power, can be applied to reflective displays and to light shutters. By coupling with a reflective polarizer the efficiency of light scattering at the focal conic texture can be enhanced.