Diesel exhaust and house dust mite allergen lead to common changes in the airway methylome and hydroxymethylome.

Exposures to diesel exhaust particles (DEP) from traffic and house dust mite (HDM) allergens significantly increase risks of airway diseases, including asthma. This negative impact of DEP and HDM may in part be mediated by epigenetic mechanisms. Beyond functioning as a mechanical barrier, airway epithelial cells provide the first line of immune defense towards DEP and HDM exposures. To understand the epigenetic responses of airway epithelial cells to these exposures, we exposed human bronchial epithelial cells to DEP and HDM and studied genome-wide 5-methyl-cytosine (5mC) and 5-hydroxy-methylcytosine (5hmC) at base resolution. We found that exposures to DEP and HDM result in elevated TET1 and DNMT1 expression, associated with 5mC and 5hmC changes. Interestingly, over 20% of CpG sites are responsive to both exposures and changes in 5mC at these sites negatively correlated with gene expression differences. These 5mC and 5hmC changes are located in genes and pathways related to oxidative stress responses, epithelial function and immune cell responses and are enriched for binding sites of transcription factors (TFs) involved in these pathways. Histone marks associated with promoters, enhancers and actively transcribed gene bodies were associated with exposure-induced DNA methylation changes. Collectively, our data suggest that exposures to DEP and HDM alter 5mC and 5hmC levels at regulatory regions bound by TFs, which coordinate with histone marks to regulate gene networks of oxidative stress responses, epithelial function and immune cell responses. These observations provide novel insights into the epigenetic mechanisms that mediate the epithelial responses to DEP and HDM in airways

The Highly Selective and Near-Quantitative Conversion of Glucose to 5-Hydroxymethylfurfural Using Ionic Liquids

A number of ionic liquids have been shown to be excellent solvents for lignocellulosic biomass processing, and some of these are particularly effective in the production of the versatile chemical building block 5-hydroxymethylfurfural (HMF). In this study, the production of HMF from the simple sugar glucose in ionic liquid media is discussed. Several aspects of the selective catalytic formation of HMF from glucose have been elucidated using metal halide salts in two distinct ionic liquids, 1-butyl-3-methylimidazolium chloride and 1-butyl-3-methylimidazolium hydrogen sulfate as well as mixtures of these, revealing key features for accelerating the desired reaction and suppressing byproduct formation. The choice of ionic liquid anion is revealed to be of particular importance, with low HMF yields in the case of hydrogen sulfate-based salts, which are reported to be effective for HMF production from fructose. The most successful system investigated in this study led to almost quantitative conversion of glucose to HMF (90% in only 30 minutes using 7 mol% catalyst loading at 120°C) in a system which is selective for the desired product, has low energy intensity and is environmentally benign

Identification and characterization of an imidazolium by-product formed during the synthesis of 4-methylmethcathinone (mephedrone)

4-Methylmethcathinone (2-methylamino-1-(4-methylphenyl)propan-1-one, mephedrone) is a psychoactive substance that has been associated with recreational use worldwide. Analytical data related to mephedrone are abundantly available but the characterization of by-products obtained during organic synthesis remains to be explored. This study presents the identification of a 1,2,3,5-tetramethyl-4-(4-methylphenyl)-1H-imidazol-3-ium salt (TMMPI), which was formed during the synthesis of mephedrone. When diethyl ether was added to the crude reaction product, solid material precipitated from the solution. Analytical characterization of TMMPI employed a range of analytical techniques including chromatographic analysis in combination with various mass spectrometric detection methods, nuclear magnetic resonance spectroscopy, and crystal structure analysis. Additional confirmation was obtained from organic synthesis of the imidazolium by-product. When TMMPI was subjected to analysis by gas chromatography-mass spectrometry (GC-MS), isomerization and degradation into two distinct compounds were observed, which pointed towards thermal instability under GC conditions. A liquid chromatography-mass spectrometry (LC-MS) based investigation into a micro-scale synthesis of mephedrone and three additional analogues revealed that the corresponding TMMPI analogue was formed. Interestingly, storage of mephedrone freebase in a number of organic solvents also gave rise to TMMPI and it appeared that its formation during storage was significantly reduced in the absence of air. The present study aimed to support clandestine forensic investigations by employing analytical strategies that are applicable to manufacturing sites. The imidazolium salts will most likely be found amongst the waste products of any clandestine lab site under investigation rather than with the desired product

Second language user support

Computer users rarely experience entirely trouble-free interaction. The natural variety ofindividuals ensures that no software systems yield constantly fluent interaction for allusers. In consequence, software designers often strive to ameliorate this situation bybuilding 'user support' into their systems. User support can take different forms but,conventionally, each aims to assist the needy end-user by means of facilities directly supporting the performance of certain operations, or through supply of information thatadvises the user on available system functionality.The present paper briefly characterises a range of user support facilities before describingone requirement in greater detail. This aspect considers the needs of users whose mother-tongue is not English, but who are obliged to use English-based information systems. Inthis context, 'helping the user' must reasonably extend beyond mere advice on systemoperation to selective elucidation of information content. We regard this move as alogical extension of the user support concept, by seeking to address specific interactionneeds in a target user population. An example of this approach is described through aninformation system, in the domain of civil engineering, for native Chinese speakers ofEnglish

Dust-free quasars in the early Universe

The most distant quasars known, at redshifts z=6, generally have properties indistinguishable from those of lower-redshift quasars in the rest-frame ultraviolet/optical and X-ray bands. This puzzling result suggests that these distant quasars are evolved objects even though the Universe was only seven per cent of its current age at these redshifts. Recently one z=6 quasar was shown not to have any detectable emission from hot dust, but it was unclear whether that indicated different hot-dust properties at high redshift or if it is simply an outlier. Here we report the discovery of a second quasar without hot-dust emission in a sample of 21 z=6 quasars. Such apparently hot-dust-free quasars have no counterparts at low redshift. Moreover, we demonstrate that the hot-dust abundance in the 21 quasars builds up in tandem with the growth of the central black hole, whereas at low redshift it is almost independent of the black hole mass. Thus z=6 quasars are indeed at an early evolutionary stage, with rapid mass accretion and dust formation. The two hot-dust-free quasars are likely to be first-generation quasars born in dust-free environments and are too young to have formed a detectable amount of hot dust around them.Comment: To be published in Nature on the 18 March 2010

Inductively guided circuits for ultracold dressed atoms

Recent progress in optics, atomic physics and material science has paved the way to study quantum effects in ultracold atomic alkali gases confined to non-trivial geometries. Multiply connected traps for cold atoms can be prepared by combining inhomogeneous distributions of DC and radio-frequency electromagnetic fields with optical fields that require complex systems for frequency control and stabilization. Here we propose a flexible and robust scheme that creates closed quasi-one-dimensional guides for ultracold atoms through the ‘dressing’ of hyperfine sublevels of the atomic ground state, where the dressing field is spatially modulated by inductive effects over a micro-engineered conducting loop. Remarkably, for commonly used atomic species (for example, 7Li and 87Rb), the guide operation relies entirely on controlling static and low-frequency fields in the regimes of radio-frequency and microwave frequencies. This novel trapping scheme can be implemented with current technology for micro-fabrication and electronic control

General Form of the Color Potential Produced by Color Charges of the Quark

Constant electric charge $e$ satisfies the continuity equation $\partial_\mu j^{\mu}(x)= 0$ where $j^\mu(x)$ is the current density of the electron. However, the Yang-Mills color current density $j^{\mu a}(x)$ of the quark satisfies the equation $D_\mu[A] j^{\mu a}(x)= 0$ which is not a continuity equation ($\partial_\mu j^{\mu a}(x)\neq 0$) which implies that a color charge $q^a(t)$ of the quark is not constant but it is time dependent where $a=1,2,...8$ are color indices. In this paper we derive general form of color potential produced by color charges of the quark. We find that the general form of the color potential produced by the color charges of the quark at rest is given by \Phi^a(x) =A_0^a(t,{\bf x}) =\frac{q^b(t-\frac{r}{c})}{r}\[\frac{{\rm exp}[g\int dr \frac{Q(t-\frac{r}{c})}{r}] -1}{g \int dr \frac{Q(t-\frac{r}{c})}{r}}\]_{ab} where $dr$ integration is an indefinite integration, ~~ $Q_{ab}(\tau_0)=f^{abd}q^d(\tau_0)$, ~~$r=|{\vec x}-{\vec X}(\tau_0)|$, ~~$\tau_0=t-\frac{r}{c}$ is the retarded time, ~~$c$ is the speed of light, ~~${\vec X}(\tau_0)$ is the position of the quark at the retarded time and the repeated color indices $b,d$(=1,2,...8) are summed. For constant color charge $q^a$ we reproduce the Coulomb-like potential $\Phi^a(x)=\frac{q^a}{r}$ which is consistent with the Maxwell theory where constant electric charge $e$ produces the Coulomb potential $\Phi(x)=\frac{e}{r}$.Comment: Final version, two more sections added, 45 pages latex, accepted for publication in JHE

Analytical characterization and pharmacological evaluation of the new psychoactive substance 4-fluoromethylphenidate (4F-MPH) and differentiation between the (±)-threo- and (±)-erythro- diastereomers

Misuse of (±)-threo-methylphenidate (methyl-2-phenyl-2-(piperidin-2-yl)acetate; Ritalin®, MPH) has long been acknowledged, but the appearance of MPH analogs in the form of ‘research chemicals’ has only emerged in more recent years. 4-Fluoromethylphenidate (4F-MPH) is one of these recent examples and this study presents the identification and analytical characterization of two powdered 4F-MPH products that were obtained from an online vendor in 2015. Interestingly, the products appeared to have originated from two distinct batches given that one product consisted of (±)-threo-4F-MPH isomers whereas the second sample consisted of a mixture of (±)-threo and (±)-erythro 4F-MPH. Monoamine transporter studies using rat brain synaptosomes revealed that the biological activity of the 4F-MPH mixture resided with the (±)-threo- and not the (±)-erythro isomers based on higher potencies determined for blockage of dopamine uptake (IC50 4F-MPHmixture = 66 nM vs. IC50 (±)-threo = 61 nM vs. IC50 (±)-erythro = 8,528 nM) and norepinephrine uptake (IC50 4F-MPHmixture = 45 nM vs. (±)-threo = 31 nM vs. IC50 (±)-erythro = 3,779 nM). In comparison, MPH was three times less potent than (±)-threo-4F-MPH at the dopamine transporter (IC50 = 131 nM) and around 2.5-times less potent at the norepinephrine transporter (IC50 = 83 nM). Both substances were catecholamine selective with IC50 values of 8,805 nM and >10,000 nM for (±)-threo-4F-MPH and MPH at the serotonin transporter. These findings suggest that the psychostimulant properties of (±)-threo-4F-MPH might be more potent in humans than MPH

The impact of childhood glaucoma on psychosocial functioning and quality of life: a review of the literature

We present a novel comprehensive literature review of studies of the psychosocial functioning (PF) and quality of life (QoL) of patients with childhood glaucoma and their caregivers. Our findings demonstrate variable study quality and approach, as well as inconsistent results relating to the association of glaucoma-specific factors and sociodemographic variables with measured PF and QoL. Future studies should focus on the development of culturally cognizant and standardized assessment tools, execution of multi-center longitudinal studies with global representation, evaluation of PF and QoL among siblings and childhood glaucoma providers, and implementation of interventions to improve patient and caregiver PF and QoL

Cigarette smoking, von Hippel–Lindau gene mutations and sporadic renal cell carcinoma

We investigated whether smoking is associated with mutations in the Von Hippel–Lindau (VHL) gene in 337 cases of sporadic renal cell carcinoma (RCC) among 120 852 people followed for 11.3 years; the findings suggest that smoking causes RCC independently of VHL gene mutations