Native interface of the SAM domain polymer of TEL

BACKGROUND: TEL is a transcriptional repressor containing a SAM domain that forms a helical polymer. In a number of hematologic malignancies, chromosomal translocations lead to aberrant fusions of TEL-SAM to a variety of other proteins, including many tyrosine kinases. TEL-SAM polymerization results in constitutive activation of the tyrosine kinase domains to which it becomes fused, leading to cell transformation. Thus, inhibitors of TEL-SAM self-association could abrogate transformation in these cells. In previous work, we determined the structure of a mutant TEL-SAM polymer bearing a Val to Glu substitution in center of the subunit interface. It remained unclear how much the mutation affected the architecture of the polymer, however. RESULTS: Here we determine the structure of the native polymer interface. To accomplish this goal, we introduced mutations that block polymer extension, producing a heterodimer with a wild-type interface. We find that the structure of the wild-type polymer interface is quite similar to the mutant structure determined previously. With the structure of the native interface, it is possible to evaluate the potential for developing therapeutic inhibitors of the interaction. We find that the interacting surfaces of the protein are relatively flat, containing no obvious pockets for the design of small molecule inhibitors. CONCLUSION: Our results confirm the architecture of the TEL-SAM polymer proposed previously based on a mutant structure. The fact that the interface contains no obvious potential binding pockets suggests that it may be difficult to find small molecule inhibitors to treat malignancies in this way

Electromagnetic detection of axions

Photon-to-axion conversions in the static electromagnetic fields are reconsidered in detail by using the Feynman diagram techniques. The differential cross sections are presented for the conversions in the presence of the electric field of the flat condenser as well as in the magnetic field of the solenoid. Based on our results a laboratory experiment for the production and the detection of the axions is described. This experiment will exploit the axion decay constant as well as the axion mass.Comment: 7 pages, latex, no figures, to appear in Phys. Lett.

Alcohol Use, Risk Taking, Leisure Activities and Health Care Use Among Young People in Northern Vietnam

Alcohol consumption is associated with a wide range of health and social consequences. It is also associated with a number of risk taking behaviours. These include illicit drug use and unsafe sex.  Alcohol consumption appears to be increasing in Vietnam. The purpose of this paper is to examine the patterns of alcohol consumption and its relationship with a number of other risk taking behaviours amongst young people.  Information was also obtained concerning leisure activities and use of health care. The paper also sets out to examine possible gender differences in relation to alcohol consumption and risk behaviour and to propose the development and implementation of alcohol monitoring and prevention programs in Vietnam.  The study involved a cross-sectional, community survey using a standardised interview.  This was conducted during face-to-face interviews with 1,408 young people aged 10-19 years.  Respondents were recruited randomly through the lists of the households from 12 selected communes in three areas in Northern Vietnam. The findings presented here were part of a larger health risk behaviour survey.  Levels of alcohol use were low. Overall, 16.5% of participants were experienced drinkers, and only 4% of them were current drinkers. Males were significantly more likely than females to report drinking. This study also showed that rates of alcohol consumption were associated with age, education, geographical area, gender, tobacco smoking, involvement in violence, watching television, computer use and playing computer games, wearing safety helmets and use of health services. Alcohol consumption tended to increase with age for both males and females.  Alcohol and its effects on young people are clearly a growing public health issue in Vietnam.  Because of this, more detailed behavioral research should be conducted into the relationship between alcohol consumption and other risky behaviours amongst young people.  It is also recommended that alcohol harm reduction policies should be implemented and integrated into measures to reduce levels of other health problems such as HIV/AIDS and non communicable diseases. Such policies should ideally be evidence-based and evaluated

Single-molecule super-resolution imaging of chromosomes and in situ haplotype visualization using Oligopaint FISH probes

Fluorescence in situ hybridization (FISH) is a powerful single-cell technique for studying nuclear structure and organization. Here we report two advances in FISH-based imaging. We first describe the in situ visualization of single-copy regions of the genome using two single-molecule super-resolution methodologies. We then introduce a robust and reliable system that harnesses single-nucleotide polymorphisms (SNPs) to visually distinguish the maternal and paternal homologous chromosomes in mammalian and insect systems. Both of these new technologies are enabled by renewable, bioinformatically designed, oligonucleotide-based Oligopaint probes, which we augment with a strategy that uses secondary oligonucleotides (oligos) to produce and enhance fluorescent signals. These advances should substantially expand the capability to query parent-of-origin-specific chromosome positioning and gene expression on a cell-by-cell basis

Radiative torque alignment: Essential Physical Processes

We study the physical processes that affect the alignment of grains subject to radiative torques (RATs). To describe the action of RATs, we use the analytical model (AMO) of RATs introduced in Paper I. We focus our discussion on the alignment by anisotropic radiation flux with respect to magnetic field, which defines the axis of grain Larmor precession. Such an alignment does not invoke paramagnetic dissipation (i.e. Davis-Greenstein mechanism), but, nevertheless, grains tend to be aligned with long axes perpendicular to the magnetic field. When we account for thermal fluctuations within grain material, we show that for grains, which are characterized by a triaxial ellipsoid of inertia, the zero-$J$ attractor point obtained in our earlier study develops into a low-$J$ attractor point. We study effects of stochastic gaseous bombardment and show that gaseous bombardment can drive grains from low-$J$ to high-$J$ attractor points in cases when the high-$J$ attractor points are present. As the alignment of grain axes with respect to angular momentum is higher for higher values of $J$, counter-intuitively, gaseous bombardment can increase the degree of grain alignment in respect to the magnetic field. We also study the effects of torques induced by H$_2$ formation and show that they can change the value of angular momentum at high-$J$ attractor point, but marginally affect the value of angular momentum at low-$J$ attractor points. We compare the AMO results with those obtained using the direct numerical calculations of RATs acting upon irregular grains and validate the use of the AMO for realistic situations of RAT alignment.Comment: 31 pages. MNRAS 2007, in press, typos are corrected

Mapping Geographic Areas of High and Low Drug Adherence in Patients Prescribed Continuing Treatment for Acute Coronary Syndrome After Discharge

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/90283/1/phco.31.10.927.pd

Galactic foregrounds: Spatial fluctuations and a procedure of removal

Present day cosmic microwave background (CMB) studies require more accurate removal of Galactic foreground emission. In this paper, we consider a way of filtering out the diffuse Galactic fluctuations on the basis of their statistical properties, namely, the power-law spectra of fluctuations. We focus on the statistical properties of two major Galactic foregrounds that arise from magnetized turbulence, namely, diffuse synchrotron emission and thermal emission from dust and describe how their power laws change with the Galactic latitude. We attribute this change to the change of the geometry of the emission region and claim that the universality of the turbulence spectrum provides a new way of removing Galactic foregrounds. We discuss and demonstrate how we can make use of our findings to remove Galactic foregrounds using a template of spatial fluctuations. In particular, we consider examples of spatial filtering of a foreground at small scales, when the separation into CMB signal and foregrounds is done at larger scales. We demonstrate that the new technique of spatial filtering of foregrounds may be promising for recovering the CMB signal in a situation when foregrounds are known at a scale different from the one under study. It can also improve filtering by combining measurements obtained at different scales.Comment: 24 pages, 12 figures, accepted to Ap

Polarization and temperature dependence of photoluminescence from zincblende and wurtzite InP nanowires

We use polarization-resolved and temperature-dependent photoluminescence of single zincblende (ZB) (cubic) and wurtzite (WZ) (hexagonal) InPnanowires to probe differences in selection rules and bandgaps between these two semiconductor nanostructures. The WZ nanowires exhibit a bandgap80meV higher in energy than the ZB nanowires. The temperature dependence of the PL is similar but not identical for the WZ and ZB nanowires. We find that ZB nanowires exhibit strong polarization parallel to the nanowire axis, while the WZ nanowires exhibit polarized emission perpendicular to the nanowire axis. This behavior is interpreted in terms of the different selection rules for WZ and ZB crystal structures.A.M., L.V.T., T.B.H., H.E.J., L.M.S., and J.M.Y.-R. acknowledge support from the Institute for Nanoscale Science and Technology of the University of Cincinnati and the National Science Foundation through Grant Nos. EEC/NUE 0532495 and ECCS 0701703. The Australian authors acknowledge support from the Australian Research Council. Y.K. acknowledges support by the Korean Science and Engineering Foundation KOSEF through Grant No. F01- 2007-000-10087-0

Natural and anthropogenic forcing of multi-decadal to centennial scale variability of sea surface temperature in the South China Sea

© The Author(s), 2021. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Goodkin, N. F., Samanta, D., Bolton, A., Ong, M. R., Hoang, P. K., Vo, S. T., Karnauskas, K. B., & Hughen, K. A. Natural and anthropogenic forcing of multi-decadal to centennial scale variability of sea surface temperature in the South China Sea. Paleoceanography and Paleoclimatology, 36(10), (2021): e2021PA004233, https://doi.org/10.1029/2021PA004233.Four hundred years of reconstructed sea surface temperatures (SSTs) from a coral located off the coast of Vietnam show significant multi-decadal to centennial-scale variability in wet and dry seasons. Wet and dry season SST co-vary significantly at multi-decadal timescales, and the Interdecadal Pacific Oscillation (IPO) explains the majority of variability in both seasons. A newly reconstructed wet season IPO index was compared to other IPO reconstructions, showing significant long-term agreement with varying amplitude of negative IPO signals based on geographic location. Dry season SST also correlates to sea level pressure anomalies and the East Asian Winter Monsoon, although with an inverse relationship from established interannual behavior, as previously seen with an ocean circulation proxy from the same coral. Centennial-scale variability in wet and dry season SST shows 300 years of near simultaneous changes, with an abrupt decoupling of the records around 1900, after which the dry season continues a long-term cooling trend while the wet season remains almost constant. Climate model simulations indicate greenhouse gases as the largest contributor to the decoupling of the wet and dry season SSTs and demonstrate increased heat advection to the western South China Sea in the wet season, potentially disrupting the covariance in seasonal SST.This research was supported by a Singapore National Research Fellowship to N.F. Goodkin (NRFF-2012-03) as administered by the Earth Observatory of Singapore and by a Singapore Ministry of Education Academic Research Fund Tier 2 award to N.F. Goodkin, K.A. Hughen, and K.B. Karnauskas (MOE-2016-T2-1-016). D. Samanta was partially supported by a Singapore Ministry of Education Tier 3 award (MOE2019-T3-1-004)

Changes in intraocular pressure in study and fellow eyes in the IVAN trial

PURPOSE: To describe changes in intraocular pressure (IOP) in the 'alternative treatments to Inhibit VEGF in Age-related choroidal Neovascularisation (IVAN)' trial (registered as ISRCTN92166560). DESIGN: Randomised controlled clinical trial with factorial design. PARTICIPANTS: Patients (n=610) with treatment naïve neovascular age-related macular degeneration were enrolled and randomly assigned to receive either ranibizumab or bevacizumab and to two regimens, namely monthly (continuous) or as needed (discontinuous) treatment. METHODS: At monthly visits, IOP was measured preinjection in both eyes, and postinjection in the study eye. OUTCOME MEASURES: The effects of 10 prespecified covariates on preinjection IOP, change in IOP (postinjection minus preinjection) and the difference in preinjection IOP between the two eyes were examined. RESULTS: For every month in trial, there was a statistically significant rise in both the preinjection IOP and the change in IOP postinjection during the time in the trial (estimate 0.02 mm Hg, 95% CI 0.01 to 0.03, p<0.001 and 0.03 mm Hg, 95% CI 0.01 to 0.04, p=0.002, respectively). There was also a small but significant increase during the time in trial in the difference in IOP between the two eyes (estimate 0.01 mm Hg, 95% CI 0.005 to 0.02, p<0.001). There were no differences between bevacizumab and ranibizumab for any of the three outcomes (p=0.93, p=0.22 and p=0.87, respectively). CONCLUSIONS: Anti-vascular endothelial growth factor agents induce increases in IOP of small and uncertain clinical significance