DNA cytosine hydroxymethylation levels are distinct among non-overlapping classes of peripheral blood leukocytes

AbstractBackgroundPeripheral blood leukocytes are the most commonly used surrogates to study epigenome-induced risk and epigenomic response to disease-related stress. We considered the hypothesis that the various classes of peripheral leukocytes differentially regulate the synthesis of 5-methylcytosine (5mCG) and its removal via Ten-Eleven Translocation (TET) dioxygenase catalyzed hydroxymethylation to 5-hydroxymethylcytosine (5hmCG), reflecting their responsiveness to environment. Although it is known that reductions in TET1 and/or TET2 activity lead to the over-proliferation of various leukocyte precursors in bone marrow and in development of chronic myelomonocytic leukemia and myeloproliferative neoplasms, the role of 5mCG hydroxymethylation in peripheral blood is less well studied.ResultsWe developed simplified protocols to rapidly and reiteratively isolate non-overlapping leukocyte populations from a single small sample of fresh or frozen whole blood. Among peripheral leukocyte types we found extreme variation in the levels of transcripts encoding proteins involved in cytosine methylation (DNMT1, 3A, 3B), the turnover of 5mC by demethylation (TET1, 2, 3), and DNA repair (GADD45A, B, G) and in the global and gene-region-specific levels of DNA 5hmCG (CD4+ T cells≫CD14+ monocytes>CD16+ neutrophils>CD19+ B cells>CD56+ NK cells>Siglec8+ eosinophils>CD8+ T cells).ConclusionsOur data taken together suggest a potential hierarchy of responsiveness among classes of leukocytes with CD4+, CD8+ T cells and CD14+ monocytes being the most distinctly poised for a rapid methylome response to physiological stress and disease

Influence of nearly resonant light on the scattering length in low-temperature atomic gases

We develop the idea of manipulating the scattering length $a$ in low-temperature atomic gases by using nearly resonant light. As found, if the incident light is close to resonance with one of the bound $p$ levels of electronically excited molecule, then virtual radiative transitions of a pair of interacting atoms to this level can significantly change the value and even reverse the sign of $a$. The decay of the gas due to photon recoil, resulting from the scattering of light by single atoms, and due to photoassociation can be minimized by selecting the frequency detuning and the Rabi frequency. Our calculations show the feasibility of optical manipulations of trapped Bose condensates through a light-induced change in the mean field interaction between atoms, which is illustrated for $^7$Li.Comment: 12 pages, 1 Postscript figur

Near Resonant Spatial Images of Confined Bose-Einstein Condensates in the '4D' Magnetic Bottle

We present quantitative measurements of the spatial density profile of Bose-Einstein condensates of sodium atoms confined in a new '4D' magnetic bottle. The condensates are imaged in transmission with near resonant laser light. We demonstrate that the Thomas-Fermi surface of a condensate can be determined to better than 1%. More generally, we obtain excellent agreement with mean-field theory. We conclude that precision measurements of atomic scattering lengths and interactions between phase separated cold atoms in a harmonic trap can be measured with high precision using this method.Comment: 15 pages, 3 figures. Submitted 10/30/97, accepted for publication in Phys. Rev. A Rapid Com

Limiting distributions for explosive PAR(1) time series with strongly mixing innovation

This work deals with the limiting distribution of the least squares estimators of the coefficients a r of an explosive periodic autoregressive of order 1 (PAR(1)) time series X r = a r X r--1 +u r when the innovation {u k } is strongly mixing. More precisely {a r } is a periodic sequence of real numbers with period P \textgreater{} 0 and such that P r=1 |a r | \textgreater{} 1. The time series {u r } is periodically distributed with the same period P and satisfies the strong mixing property, so the random variables u r can be correlated

A crossover randomised controlled trial of oral mandibular advancement devices for obstructive sleep apnoea-hypopnoea (TOMADO)

Rationale Mandibular advancement devices (MADs) are used to treat obstructive sleep apnoea-hypopnoea syndrome (OSAHS) but evidence is lacking regarding their clinical and cost-effectiveness in less severe disease. Objectives To compare clinical- and cost-effectiveness of a range of MADs against no treatment in mild to moderate OSAHS. Measurements and methods This open-label, randomised, controlled, crossover trial was undertaken at a UK sleep centre. Adults with Apnoea-Hypopnoea Index (AHI) 5–<30/h and Epworth Sleepiness Scale (ESS) score ≥9 underwent 6 weeks of treatment with three nonadjustable MADs: self-moulded (SleepPro 1; SP1); semi-bespoke (SleepPro 2; SP2); fully-bespoke MAD (bMAD); and 4 weeks no treatment. Primary outcome was AHI scored by a polysomnographer blinded to treatment. Secondary outcomes included ESS, quality of life, resource use and cost. Main results 90 patients were randomised and 83 were analysed. All devices reduced AHI compared with no treatment by 26% (95% CI 11% to 38%, p=0.001) for SP1, 33% (95% CI 24% to 41%) for SP2 and 36% (95% CI 24% to 45%, p<0.001) for bMAD. ESS was 1.51 (95% CI 0.73 to 2.29, p<0.001, SP1) to 2.37 (95% CI 1.53 to 3.22, p<0.001, bMAD) lower than no treatment (p<0.001 for all). Compliance was lower for SP1, which was the least preferred treatment at trial exit. All devices were cost-effective compared with no treatment at a £20 000/quality-adjusted life year (QALY) threshold. SP2 was the most cost-effective up to £39 800/QALY. Conclusions Non-adjustable MADs achieve clinically important improvements in mild to moderate OSAHS and are cost-effective

A stationary source of non-classical or entangled atoms

A scheme for generating continuous beams of atoms in non-classical or entangled quantum states is proposed and analyzed. For this the recently suggested transfer technique of quantum states from light fields to collective atomic excitation by Stimulated Raman adiabatic passage [M.Fleischhauer and M.D. Lukin, Phys.Rev.Lett. 84, 5094 (2000)] is employed and extended to matter waves

Optical Confinement of a Bose-Einstein Condensate

Bose-Einstein condensates of sodium atoms have been confined in an optical dipole trap using a single focused infrared laser beam. This eliminates the restrictions of magnetic traps for further studies of atom lasers and Bose-Einstein condensates. More than five million condensed atoms were transferred into the optical trap. Densities of up to $3 \times 10^{15} cm^{-3}$ of Bose condensed atoms were obtained, allowing for a measurement of the three-body decay rate constant for sodium condensates as $K_3 = (1.1 \pm 0.3) \times 10^{-30} cm^6 s^{-1}$. At lower densities, the observed 1/e lifetime was more than 10 sec. Simultaneous confinement of Bose-Einstein condensates in several hyperfine states was demonstrated.Comment: 5 pages, 4 figure

Rotational master equation for cold laser-driven molecules

The equations of motion for the molecular rotation are derived for vibrationally cold dimers that are polarized by off-resonant laser light. It is shown that, by eliminating electronic and vibrational degrees of freedom, a quantum master equation for the reduced rotational density operator can be obtained. The coherent rotational dynamics is caused by stimulated Raman transitions, whereas spontaneous Raman transitions lead to decoherence in the motion of the quantized angular momentum. As an example the molecular dynamics for the optical Kerr effect is chosen, revealing decoherence and heating of the molecular rotation.Comment: 11 pages, 5 figures, to appear in Phys. Rev.

Facial expressions depicting compassionate and critical emotions: the development and validation of a new emotional face stimulus set

Attachment with altruistic others requires the ability to appropriately process affiliative and kind facial cues. Yet there is no stimulus set available to investigate such processes. Here, we developed a stimulus set depicting compassionate and critical facial expressions, and validated its effectiveness using well-established visual-probe methodology. In Study 1, 62 participants rated photographs of actors displaying compassionate/kind and critical faces on strength of emotion type. This produced a new stimulus set based on N = 31 actors, whose facial expressions were reliably distinguished as compassionate, critical and neutral. In Study 2, 70 participants completed a visual-probe task measuring attentional orientation to critical and compassionate/kind faces. This revealed that participants lower in self-criticism demonstrated enhanced attention to compassionate/kind faces whereas those higher in self-criticism showed no bias. To sum, the new stimulus set produced interpretable findings using visual-probe methodology and is the first to include higher order, complex positive affect displays

Linear and nonlinear optical properties of the conjugated polymers PPV and MEH-PPV

We have used absorption and electroabsorption spectroscopy to investigate the electronic structure of poly(para-phenylene vinylene) (PPV) and poly (2-methoxy, 5-(2'-(ethyl)hexyloxy)-p-phenylene vinylene) (MEH-PPV). In particular we examine the often used assumption that the electronic structure of PPV and its dialkoxy substituted derivatives are essentially the same. The absorption spectrum of PPV consists of three peaks, while that of MEH-PPV has four peaks. We discuss the controversial origin of the extra peak as well as evidence for Davydov splitting effects in the absorption spectrum of PPV. The analysis of the nonlinear spectra shows further differences between the two materials. First, the binding energy of the 1B(u) exciton for PPV is some 0.1 eV higher than for MEH-PPV. Second, the peak value of Im{chi((3))(-omega;0,0,omega)} for PPV is approximately 40 times higher than that of MEH-PPV. We also found that the sum-over-states modeling of the electroabsorption spectra indicates that the transition dipole moment between the mA(g) and nB(u) states is of opposite sign in the two polymers. [S0163-1829(99)02523-0]