Inhibition of AlkB Nucleic Acid Demethylases: Promising New Epigenetic Targets

The AlkB family of nucleic acid demethylases is currently of intense chemical, biological, and medical interest because of its critical roles in several key cellular processes, including epigenetic gene regulation, RNA metabolism, and DNA repair. Emerging evidence suggests that dysregulation of AlkB demethylases may underlie the pathogenesis of several human diseases, particularly obesity, diabetes, and cancer. Hence there is strong interest in developing selective inhibitors for these enzymes to facilitate their mechanistic and functional studies and to validate their therapeutic potential. Herein we review the remarkable advances made over the past 20 years in AlkB demethylase inhibition research. We discuss the rational design of reported inhibitors, their mode-of-binding, selectivity, cellular activity, and therapeutic opportunities. We further discuss unexplored structural elements of the AlkB subfamilies and propose potential strategies to enable subfamily selectivity. It is hoped that this perspective will inspire novel inhibitor design and advance drug discovery research in this field

Quantum states for perfectly secure secret sharing

In this work, we investigate what kinds of quantum states are feasible to perform perfectly secure secret sharing, and present its necessary and sufficient conditions. We also show that the states are bipartite distillable for all bipartite splits, and hence the states could be distillable into the Greenberger-Horne-Zeilinger state. We finally exhibit a class of secret-sharing states, which have an arbitrarily small amount of bipartite distillable entanglement for a certain split.Comment: 4 page

Silica grain catalysis of methanol formation

The specific catalytic effect of a silica grain on the formation of methanol via the sequential addition of H atoms to CO adsorbed on the surface is investigated. A negatively charged defect on a siliceous edingtonite surface is found to reduce the gas phase barriers for the H + COads and H + H2C=O-ads reactions by 770 and 399 K, respectively, when compared to the same reactions in the gas phase. The catalytic effect of negatively charged surface sites could also be applicable to the hydrogenation of other adsorbed unsaturated species. However, the activation energies on the surface defect are still too large (1150 and 2230 K) for CH3OH to form efficiently at 10-20 K in the interstellar medium via a classical mechanism. It is therefore suggested that quantum mechanical tunnelling through the activation barrier is required for these hydrogen addition reactions to proceed at such temperatures. The calculations show that because the adsorption energies of CO and H2C=O on the negatively charged defect are substantial, CH3OH may form efficiently during the warm-up period in star-forming regions

Polymer Translocation in Crowded Environments

We study the effect of the crowded nature of the cellular cytoplasm on the translocation of a polymer through a pore in a membrane. By systematically treating the entropic penalty due to crowding, we show that the translocation dynamics are significantly altered, leading to novel scaling behaviors of the translocation time in terms of chain length. We also observe new and qualitatively different translocation regimes depending upon the extent of crowding, transmembrane chemical potential asymmetry, and polymer length.Comment: 4 figure

Climatology of water vapor in the upper troposphere and lower stratosphere determined from Sage 2 observations

The purpose of this paper is to present a vertically-resolved global climatology of water vapor in the upper troposphere and lower stratosphere based on multi-year SAGE 2 observations. Seasonally averaged zonal mean profiles are illustrated in terms of both mixing ration and relative humidity

Improved synthesis of 4-[18F]fluoro-m-hydroxyphenethylguanidine using an iodonium ylide precursor

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/151961/1/jlcr3791.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/151961/2/jlcr3791_am.pd

Factor structure of the Malay-version Generalized Anxiety Disorder-7 (GAD-7) questionnaire among patients with diabetes mellitus

The Malay-version Generalised Anxiety Disorder-7 (GAD-7) questionnaire previously demonstrated good concurrent validity, i.e. sensitivity and specificity as a screening instrument for anxiety. However, its psychometric properties on factorial validity had not been further investigated. This study investigated the factor structure of the Malay-version GAD-7 in among 300 diabetic outpatients (mean age: 60.4 years, SD: 13.4 years; 52.7% male) in a Malaysian university hospital in Kuala Lumpur. Study participants completed questionnaires on sociodemographic information, the GAD-7, the Beck’s Depression Inventory (BDI), and the WHOQOL-BREF instrument. The Malay-version GAD-7 displayed good internal consistency (Cronbach’s α=0.91) and satisfactory convergent validity with depression (Pearson’s R=0.642, p1 (eigenvalue=4.614), suggesting a unidimensional factor structure. All seven items were loaded on a higher-order factor (‘generalized anxiety’) in confirmatory factor analysis. This model did not have a good fit with the data. After examining the modification indices, the model was respecified to allow covariance of the error terms of items 1 and 2, and 2 and 3. The respecified model appeared to fit the data better (χ2=35.216, df=12, p<0.001, CFI=0.98, TLI=0.97, RMSEA=0.08, and AIC=67.22). The findings suggested that items 1, 2 and 3 of GAD-7 may share distinctive variance out of that explained by the ‘generalized anxiety’ factor. Overall, the Malay-version GAD-7 appeared to be a valid measurement of the symptoms of anxiety in this study

Probing the Spatial Distribution of Extrasolar Planets with Gravitational Microlensing

Under the current microlensing planet search strategy of monitoring events caused by stellar-mass lenses, only planets located within a narrow region of separations from central stars can be effectively detected. However, with the dramatic increase of the monitoring frequency, two additional populations of free-floating and wide-orbit planets can be detected. In this paper, we investigate the lensing properties of events caused by wide-orbit planets and find that the light curves of a significant fraction of these events will exhibit signatures of central stars, enabling one to distinguish them from those caused by free-floating planets. Due to the large primary/planet mass ratio, the effect of the central star endures to considerable separations. We find that for a Jupiter-mass planet the signatures of the central star can be detected with fractional deviations of > 5% from the best-fitting single-lens light curves for > 80% of events caused by bound planets with separations < 10 AU and the probability is still substantial for planets with separations up to 20 AU. Therefore, detecting a large sample of these events will provide useful information about the distribution of extrasolar planets around their central stars. Proper estimation of the probability of distinguishing events caused by wide-orbit planets from those caused by free-floating planets will be important for the correct determination of the frequency of free-floating planets, whose microlensing sample will be contaminated by wide-orbits planets.Comment: total 7 pages, including 4 figures, ApJ, submitte

Raman Scattered He II λ\lambda 6545 Line in the Symbiotic Star V1016 Cygni

We present a spectrum of the symbiotic star V1016 Cyg observed with the 3.6 m Canada-France-Hawaii Telescope, in order to illustrate a method to measure the covering factor of the neutral scattering region around the giant component with respect to the hot emission region around the white dwarf component. In the spectrum, we find broad wings around H$\alpha$ and a broad emission feature around 6545${\rm \AA}$ that is blended with the [N II]$\lambda$ 6548 line. These two features are proposed to be formed by Raman scattering by atomic hydrogen, where the incident radiation is proposed to be UV continuum radiation around Ly$\beta$ in the former case and He II $\lambda$ 1025 emission line arising from $n=6\to n=2$ transitions for the latter feature. We remove the H$\alpha$ wings by a template Raman scattering wing profile and subtract the [N II] $\lambda$ 6548 line using the 3 times stronger [N II] $\lambda$ 6583 feature in order to isolate the He II Raman scattered 6545 \AA line. We obtain the flux ratio $F_{6545}/F_{6560}=0.24$ of the He II $\lambda$ 6560 emission line and the 6545 \AA feature for V1016 Cyg. Under the assumption that the He II emission from this object is isotropic, this ratio is converted to the ratio $\Phi_{6545}/\Phi_{1025}=0.17$ of the number of the incident photons and that of the scattered photons. This implies that the scattering region with H I column density $N_{HI}\ge 10^{20}{\rm cm^{-2}}$ covers 17 per cent of the emission region. By combining the presumed binary period $\sim 100$ yrs of this system we infer that a significant fraction of the slow stellar wind from the Mira component is ionized and that the scattering region around the Mira extends a few tens of AU, which is closely associated with the mass loss process of the Mira component.Comment: 12 pages, 6 figures, accepted for publication in Ap