Genomic analysis of cohesin dynamics in fission yeast

Cohesin holds sister chromatids together and facilitates their accurate segregation in mitosis. Little is known about how and where cohesin binds to chromosomes. Recent genome-wide investigations have led to apparent disparities between different model organisms. In this thesis, analysis of the cohesin binding pattern reveals that several determinants, thought specific for distinct organisms, collectively define the overall distribution of cohesin along fission yeast chromosomes. Like in budding yeast, cohesin is mainly detected at sites of convergent transcriptional termination, in the following termed convergent sites. However, only approximately half of these are bound whereas in budding yeast almost all of them are associated with cohesin. Furthermore, we detect cohesin at loci away from convergent sites which are characterised by the presence of the cohesin loader Mis4/Ssl3. Cohesin loading sites show a striking overlap with strongly transcribed genes, including tRNA and ribosomal protein genes. This is reminiscent of Drosophila cohesin and its loading factor Nipped-B that both overlap near highly transcribed genes. The cohesin loader also promotes cohesin accumulation at neighbouring convergent sites, which, together with gene arrangement and transcription, contributes to the distribution of cohesin among convergent sites. Cohesin binding to G1 chromosomes depends on the continuous activity of the cohesin loader Mis4/Ssl3. Cohesin stability then increases during S phase independently of DNA replication but in part dependent on the acetyltransferase Eso1, a factor implicated in the establishment of cohesion. This indicates that cohesin stabilisation might be a pre-requisite for cohesion establishment rather than its consequence. During mitosis, a fraction of cohesin leaves chromosomes in a cleavage-independent reaction in prophase similarly to what has been observed in higher eukaryotes. A substantial pool of cohesin then dissociates from chromosomes upon its cleavage at anaphase onset. As a unique feature, centromeric cohesin spreads out onto chromosome arms towards anaphase as the heterochromatin protein Swi6 dissociates from centromeres. Taken together, our results suggest conserved mechanisms for both cohesin binding and dynamics across eukaryotes

Ultrafast carrier relaxation in GaN, In_(0.05)Ga_(0.95)N and an In_(0.05)Ga_(0.95)/In_(0.15)Ga_(0.85)N Multiple Quantum Well

Room temperature, wavelength non-degenerate ultrafast pump/probe measurements were performed on GaN and InGaN epilayers and an InGaN multiple quantum well structure. Carrier relaxation dynamics were investigated as a function of excitation wavelength and intensity. Spectrally-resolved sub-picosecond relaxation due to carrier redistribution and QW capture was found to depend sensitively on the wavelength of pump excitation. Moreover, for pump intensities above a threshold of 100 microJ/cm2, all samples demonstrated an additional emission feature arising from stimulated emission (SE). SE is evidenced as accelerated relaxation (< 10 ps) in the pump-probe data, fundamentally altering the re-distribution of carriers. Once SE and carrier redistribution is completed, a slower relaxation of up to 1 ns for GaN and InGaN epilayers, and 660 ps for the MQW sample, indicates carrier recombination through spontaneous emission.Comment: submitted to Phys. Rev.

Quantum optical coherence tomography with dispersion cancellation

We propose a new technique, called quantum optical coherence tomography (QOCT), for carrying out tomographic measurements with dispersion-cancelled resolution. The technique can also be used to extract the frequency-dependent refractive index of the medium. QOCT makes use of a two-photon interferometer in which a swept delay permits a coincidence interferogram to be traced. The technique bears a resemblance to classical optical coherence tomography (OCT). However, it makes use of a nonclassical entangled twin-photon light source that permits measurements to be made at depths greater than those accessible via OCT, which suffers from the deleterious effects of sample dispersion. Aside from the dispersion cancellation, QOCT offers higher sensitivity than OCT as well as an enhancement of resolution by a factor of 2 for the same source bandwidth. QOCT and OCT are compared using an idealized sample.Comment: 19 pages, 4 figure

Spectral properties of the dimerized and frustrated S=1/2S=1/2 chain

Spectral densities are calculated for the dimerized and frustrated S=1/2 chain using the method of continuous unitary transformations (CUTs). The transformation to an effective triplon model is realized in a perturbative fashion up to high orders about the limit of isolated dimers. An efficient description in terms of triplons (elementary triplets) is possible: a detailed analysis of the spectral densities is provided for strong and intermediate dimerization including the influence of frustration. Precise predictions are made for inelastic neutron scattering experiments probing the S=1 sector and for optical experiments (Raman scattering, infrared absorption) probing the S=0 sector. Bound states and resonances influence the important continua strongly. The comparison with the field theoretic results reveals that the sine-Gordon model describes the low-energy features for strong to intermediate dimerization only at critical frustration.Comment: 21 page

Association of Prenatal Maternal Depression and Anxiety Symptoms with Infant White Matter Microstructure

Importance: Maternal depression and anxiety can have deleterious and lifelong consequences on child development. However, many aspects of the association of early brain development with maternal symptoms remain unclear. Understanding the timing of potential neurobiological alterations holds inherent value for the development and evaluation of future therapies and interventions. Objective: To examine the association between exposure to prenatal maternal depression and anxiety symptoms and offspring white matter microstructure at 1 month of age. Design, Setting, and Participants: This cohort study of 101 mother-infant dyads used a composite of depression and anxiety symptoms measured in mothers during the third trimester of pregnancy and measures of white matter microstructure characterized in the mothers' 1-month offspring using diffusion tensor imaging and neurite orientation dispersion and density imaging performed from October 1, 2014, to November 30, 2016. Magnetic resonance imaging was performed at an academic research facility during natural, nonsedated sleep. Main Outcomes and Measures: Brain mapping algorithms and statistical models were used to evaluate the association between maternal depression and anxiety and 1-month infant white matter microstructure as measured by diffusion tensor imaging and neurite orientation dispersion and density imaging findings. Results: In the 101 mother-infant dyads (mean [SD] age of mothers, 33.22 [3.99] years; mean age of infants at magnetic resonance imaging, 33.07 days [range, 18-50 days]; 92 white mothers [91.1%]; 53 male infants [52.5%]), lower 1-month white matter microstructure (decreased neurite density and increased mean, radial, and axial diffusivity) was associated in right frontal white matter microstructure with higher prenatal maternal symptoms of depression and anxiety. Significant sex × symptom interactions with measures of white matter microstructure were also observed, suggesting that white matter development may be differentially sensitive to maternal depression and anxiety symptoms in males and females during the prenatal period. Conclusions and Relevance: These data highlight the importance of the prenatal period to early brain development and suggest that the underlying white matter microstructure is associated with the continuum of prenatal maternal depression and anxiety symptoms

Fractional S^z excitation and its bound state around the 1/3 plateau of the S=1/2 Ising-like zigzag XXZ chain

We present the microscopic view for the excitations around the 1/3 plateau state of the Ising-like zigzag XXZ chain. We analyze the low-energy excitations around the plateau with the degenerating perturbation theory from the Ising limit, combined with the Bethe-form wave function. We then find that the domain-wall particles carrying $S^z=\pm 1/3$ and its bound state of $S^z=\pm 2/3$ describe well the low-energy excitations around the 1/3 plateau state. The formation of the bound state of the domain-walls clearly provides the microscopic mechanism of the cusp singularities and the even-odd behavior in the magnetization curve.Comment: 13 pages, 15 figure

Critical properties of 1-D spin 1/2 antiferromagnetic Heisenberg model

We discuss numerical results for the 1-D spin 1/2 antiferromagnetic Heisenberg model with next-to-nearest neighbour coupling and in the presence of an uniform magnetic field. The model develops zero frequency excitations at field dependent soft mode momenta. We compute critical quantities from finite size dependence of static structure factors.Comment: talk given by H. Kr{\"o}ger at Heraeus Seminar Theory of Spin Lattices and Lattice Gauge Models, Bad Honnef (1996), 20 pages, LaTeX + 18 figures, P

Co-creation of Value in IT Service Processes Using Semantic MediaWiki

Abstract: Enterprises are substituting their own IT-Systems by services provided by external providers. This provisioning of services may be done in an industrialized way, separating the service provider from the consumer. However, using industrialized services diminishes the capability to differentiate from competitors. To counter this, collaborative service processes based on the co-creation of value between service providers and prosumers are of huge importance. The approach presented shows how the co-creation of value in IT-service processes can profit from social software, using the example of the Semantic MediaWiki

The T2K ND280 Off-Axis Pi-Zero Detector

The Pi-Zero detector (P{\O}D) is one of the subdetectors that makes up the off-axis near detector for the Tokai-to-Kamioka (T2K) long baseline neutrino experiment. The primary goal for the P{\O}D is to measure the relevant cross sections for neutrino interactions that generate pi-zero's, especially the cross section for neutral current pi-zero interactions, which are one of the dominant sources of background to the electron neutrino appearance signal in T2K. The P{\O}D is composed of layers of plastic scintillator alternating with water bags and brass sheets or lead sheets and is one of the first detectors to use Multi-Pixel Photon Counters (MPPCs) on a large scale.Comment: 17 pages, submitted to NIM

On the Mechanism of Hyperthermia-Induced BRCA2 Protein Degradation

The DNA damage response (DDR) is a designation for a number of pathways that protects our DNA from various damaging agents. In normal cells, the DDR is extremely important for maintaining genome integrity, but in cancer cells these mechanisms counteract therapy-induced DNA damage. Inhibition of the DDR could therefore be used to increase the efficacy of anti-cancer treatments. Hyperthermia is an example of such a treatment—it inhibits a sub-pathway of the DDR, called homologous recombination (HR). It does so by inducing proteasomal degradation of BRCA2 —one of the key HR factors. Understanding the precise mechanism that mediates this degradation is important for our understanding of how hyperthermia affects therapy and how homologous recombination and BRCA2 itself function. In addition, mechanistic insight into the process of hyperthermia-induced BRCA2 degradation can yield new therapeutic strategies to enhance the effects of local hyperthermia or to inhibit HR. Here, we investigate the mechanisms driving hyperthermia-induced BRCA2 degradation. We find that BRCA2 degradation is evolutionarily conserved, that BRCA2 stability is dependent on HSP90, that ubiquitin might not be involved in directly targeting BRCA2 for protein degradation via the proteasome, and that BRCA2 degradation might be modulated by oxidative stress and radical scavengers