De novo DNA demethylation and non-coding transcription define active intergenic regulatory elements

Deep sequencing of mammalian DNA methylomes has uncovered a previously unpredicted number of discrete hypomethylated regions in intergenic space (iHMRs). Here, we combined whole genome bisulfite sequencing data with extensive gene-expression and chromatin-state data to define functional classes of iHMRs, and to reconstruct the dynamics of their establishment in a developmental setting. Comparing HMR profiles in embryonic stem and primary blood cells, we show that iHMRs mark an exclusive subset of active DNase hypersensitive sites (DHS), and that both developmentally constitutive and cell-type specific iHMRs display chromatin states typical of distinct regulatory elements. We also observe that iHMR changes are more predictive of nearby gene activity than the promoter HMR itself, and that expression of non-coding RNAs within the iHMR accompanies full activation and complete demethylation of mature B cell enhancers. Conserved sequence features corresponding to iHMR transcript start sites, including a discernable TATAA motif, suggest a conserved, functional role for transcription in these regions. Similarly, we explored both primate-specific and human-population variation at iHMRs, finding that while enhancer iHMRs are more variable in sequence and methylation status than any other functional class, conservation of the TATA box is highly predictive of iHMR maintenance, reflecting the impact of sequence plasticity and transcriptional signals on iHMR establishment. Overall, our analysis allowed us to construct a 3-step timeline in which 1) intergenic DHS are pre-established in the stem cell, 2) partial demethylation of blood specific intergenic DHSs occurs in blood progenitors, and 3) complete iHMR formation and transcription coincide with enhancer activation in lymphoid-specified cells

Harmonically Resonant Cavity as a Bunch-Length Monitor

A compact, harmonically resonant cavity with fundamental resonant frequency 1497 MHz was used to evaluate the temporal characteristics of electron bunches produced by a 130 kV dc high voltage spin-polarized photoelectron source at the Continuous Electron Beam Accelerator Facility (CEBAF) photoinjector, delivered at 249.5 and 499 MHz repetition rates and ranging in width from 45 to 150 picoseconds (FWHM). A cavity antenna attached directly to a sampling oscilloscope detected the electron bunches as they passed through the cavity bore with a sensitivity of ∼1  mV/μA . The oscilloscope waveforms are a superposition of the harmonic modes excited by the beam, with each cavity mode representing a term of the Fourier series of the electron bunch train. Relatively straightforward post-processing of the waveforms provided a near-real time representation of the electron bunches revealing bunch-length and the relative phasing of interleaved beams. The noninvasive measurements from the harmonically resonant cavity were compared to measurements obtained using an invasive RF-deflector-cavity technique and to predictions from particle tracking simulations

Characterization of Dicer-deficient murine embryonic stem cells

Dicer is an RNase III-family nuclease that initiates RNA interference (RNAi) and related phenomena by generation of the small RNAs that determine the specificity of these gene silencing pathways. We have previously shown that Dicer is essential for mammalian development, with Dicer-deficient mice dying at embryonic day 7.5 with a lack of detectable multipotent stem cells. To permit a more detailed investigation of the biological roles of Dicer, we have generated embryonic stem cell lines in which their single Dicer gene can be conditionally inactivated. As expected, Dicer loss compromises maturation of microRNAs and leads to a defect in gene silencing triggered by long dsRNAs. However, the absence of Dicer does not affect the ability of small interfering RNAs to repress gene expression. Of interest, Dicer loss does compromise the proliferation of ES cells, possibly rationalizing the phenotype previously observed in Dicer-null animals. Dicer loss also affects the abundance of transcripts from mammalian centromeres but does so without a pronounced affect on histone modification status at pericentric repeats or methylation of centromeric DNA. These studies provide a conditional model of RNAi deficiency in mammals that will permit the dissection of the biological roles of the RNAi machinery in cultured mammalian cells

Genomic landscape of human allele-specific DNA methylation

DNA methylation mediates imprinted gene expression by passing an epigenomic state across generations and differentially marking specific regulatory regions on maternal and paternal alleles. Imprinting has been tied to the evolution of the placenta in mammals and defects of imprinting have been associated with human diseases. Although recent advances in genome sequencing have revolutionized the study of DNA methylation, existing methylome data remain largely untapped in the study of imprinting. We present a statistical model to describe allele-specific methylation (ASM) in data from high-throughput short-read bisulfite sequencing. Simulation results indicate technical specifications of existing methylome data, such as read length and coverage, are sufficient for fullgenome ASM profiling based on our model. We used our model to analyze methylomes for a diverse set of human cell types, including cultured and uncultured differentiated cells, embryonic stem cells and induced pluripotent stem cells. Regions of ASM identified most consistently across methylomes are tightly connected with known imprinted genes and precisely delineate the boundaries of several known imprinting control regions. Predicted regions of ASM common to multiple cell types frequently mark noncoding RNA promoters and represent promising starting points for targeted validation. More generally, our model provides the analytical complement to cutting-edge experimental technologies for surveying ASM in specific cell types and across species

Harmonically Resonant Cavity as a Bunch Length Monitor

A compact, harmonically-resonant cavity with a fundamental resonant frequency of 1497 MHz was used to evaluate the temporal characteristics of electron bunches produced by a 130 kV dc high voltage spin-polarized photoelectron source at the Continuous Beam Accelerator Facility (CEBAF) photoinjector, delivered at 249.5 and 499 MHz repetition rates and ranging in width from 45 to 150 picoseconds (FWHM). The cavity’s antenna was attached directly to a sampling oscilloscope that detected the electron bunches as they passed through the cavity bore with a sensitivity of ~ mV/ μA. The oscilloscope wave-forms are a superposition of the harmonic modes excited by the beam, with each cavity mode representing a term of the Fourier series of the electron bunch train. Relatively straitforward post-processing of the waveforms provided a near-real time representation of the electron bunches revealing bunchlength and the relative phasing of interleaved beams. The non-invasive measurements from the harmonically-resonant cavity were compared to measurements obtained using an invasive rf-deflector-cavity technique and to predictions from particle tracking simulations

Orbitally Degenerate Spin-1 Model for Insulating V2O3

Motivated by recent neutron, X-ray absorption and resonant scattering experiments, we revisit the electronic structure of V2O3. We propose a model in which S=1 V3+ ions are coupled in the vertical V-V pairs forming two-fold orbitally degenerate configurations with S=2. Ferro-orbital ordering of the V-V pairs gives a description which is consistent with all experiments in the antiferromagnetic insulating phase.Comment: 4 pages, including three figure

Relativistic theory of magnetic scattering of x rays: Application to ferromagnetic iron

We present a detailed description of a first-principles formalism for magnetic scattering of circularly polar- ized x rays from solids in the framework of the fully relativistic spin-polarized multiple-scattering theory. The scattering amplitudes are calculated using a standard time-dependent perturbation theory to second order in the electron-photon interaction vertex. Particular attention is paid to understanding the relative importance of the positive- and negative-energy solutions of the Dirac equation to the scattering amplitude. The advantage of the present theory as compared with other recent works on magnetic x-ray scattering is that, being fully relativistic, spin-orbit coupling and spin-polarization effects are treated on an equal footing. Second, the electron Green’s function expressed in terms of the path operators in the multiple-scattering theory allows us to include the contribution of the crystalline environment to the scattering amplitude. To illustrate the use of the method we have done calculations on the anomalous magnetic scattering at the K , L_II , and L_III absorption edges of ferromagnetic iron

Space Charge Study of the Jefferson Lab Magnetized Electron Beam

Magnetized electron cooling could result in high luminosity at the proposed Jefferson Lab Electron-Ion Collider (JLEIC). In order to increase the cooling efficiency, a bunched electron beam with high bunch charge and high repetition rate is required. We generated magnetized electron beams with high bunch charge using a new compact DC high voltage photo-gun biased at -300 kV with alkali-antimonide photocathode and a commercial ultrafast laser. This contribution explores how magnetization affects space charge dominated beams as a function of magnetic field strength, gun high voltage, laser pulse width, and laser spot size

Experiências de contacto dos bebés com a linguagem escrita

The purpose of this study is to characterize the literacy experiences ofbabies aged between 14 and 24 months. In this study, four issues were analysed: which type of written language experiences are offered to the children, how parents value these literacy experiences, the way parents perceive their own role in the literacy development of their children and what parents know about their means of contributing to the literacy development of their children. Six mothers were interviewed. These interviews were analysed with the use of a categorical content analysis. The results suggest that mothers value and include in their practices facilitative and mediation actions of literacy experiences with their children, noting some variability depending on the respective qualifications.Este estudo exploratório visa descrever as experiências de literacia de bebés entre os 14 e os 25 meses. Analisamse quatro questões, que experiências envolvendo a linguagem escrita no seio familiar são proporcionadas aos bebés, qual o valor que os pais lhes atribuem, como percepcionam o seu papel na promoção do desenvolvimento literácito dos filhos e como podem contribuir para o desenvolvimento da literacia dos mesmos. Adotou-se uma metodologia qualitativa, com recurso à análise de conteúdo categorial das respostas dadas por seis mães em entrevista individual e semiestruturada. Concluiu-se que estas mães valorizam e incluem nas suas práticas ações facilitadoras e de mediação de experiências de literacia por parte dos seus bebés, notando-se alguma variabilidade em função das respetivas habilitações académicas.(undefined)info:eu-repo/semantics/publishedVersio

A survey of birth order status of students studying for medical degree at the University of Sheffield.

Objective It is hypothesised that firstborn children and only children are more intelligent with higher intelligence scores having been observed in firstborn or only children. Evidence of the increased intelligence has been suggested by the fact that 21/23 (91%) of US astronauts, 23/43 (53%) of US presidents and between 75 and 80% of students at Harvard are firstborn or only children. It is of interest to investigate, therefore, whether a high achieving career such as medicine has a disproportionate number of firstborn or only children. Design A survey of medical students. Setting The University of Sheffield Medical School. Participants All students studying medicine in the academic year 2011–2012. Main outcome measures The proportion of firstborn or only children. Results There was a disproportionate number of students who were firstborn or only children: 53% (95% CI 49 to 58%). The expected percentage is 39.8% and therefore we can reject the null hypothesis. The results were consistent across all phases of study. Conclusions There is a higher than expected proportion of medical students at the University of Sheffield who are firstborn or only children. The data though highlight the issue of comparing populations. Here we are comparing a population of medical students with a general population. A comparison which may not be appropriate as medical students may be drawn from a subsample of the general population