Chromosome-Biased Binding and Function of C. elegans DRM Complex, and Its Role in Germline Sex-Silencing: A Dissertation

DRM is a conserved transcription factor complex that includes E2F/DP and pRB family proteins and plays important roles in the cell cycle and cancer. Recent work has unveiled a new aspect of DRM function in regulating genes involved in development and differentiation. These studies, however, were performed with cultured cells and a genome-wide study involving intact organisms undergoing active proliferation and differentiation was lacking. Our goal was to extend the knowledge of the role of DRM in gene regulation through development and in multiple tissues. To accomplish this, we employed genomic approaches to determine genome-wide targets of DRM using the nematode Caenorhabditis elegans as a model system. In this dissertation, I focus on the DRM component LIN-54 since it was proposed to exhibit DNA-binding activity. First, we confirmed the DNA-binding activity of C.elegans LIN-54 in vivo, and showed it is essential to recruit the DRM complex to its target genes. Next, chromatin immunoprecipitation and gene expression profiling revealed that LIN-54 controls transcription of genes implicated in cell division, development and reproduction. This work identified an interesting contrast in DRM function in soma vs. germline: DRM promotes transcription of germline-specific genes in the germline, but prevents their ectopic expression in the soma. Furthermore, we discovered a novel characteristic of DRM, sex chromosome-biased binding and function. We demonstrated that C. elegans DRM preferentially binds autosomes, yet regulates X-chromosome silencing by counteracting the H3K36 histone methyltransferase MES-4. By using genomics, cytology, and genetics, we defined DRM as an important player in the regulation of germline X-chromosome gene expression, and addressed molecular mechanisms vii behind the antagonistic interactions between DRM and MES-4. I present a model to explain the interplay of DRM and MES-4, and propose a novel function of DRM and MES-4 in maintaining proper chromosome gene expression dosage. This work extends our knowledge of the conserved roles of DRM in development, and provides a new view of differing DRM functions in soma versus germline. Furthermore, we defined a novel chromosome-specific aspect of DRM-mediated regulation

In-situ growth of superconducting NdFeAs(O,F) thin films by Molecular Beam Epitaxy

The recently discovered high temperature superconductor F-doped LaFeAsO and related compounds represent a new class of superconductors with the highest transition temperature (Tc) apart from the cuprates. The studies ongoing worldwide are revealing that these Fe-based superconductors are forming a unique class of materials that are interesting from the viewpoint of applications. To exploit the high potential of the Fe-based superconductors for device applications, it is indispensable to establish a process that enables the growth of high quality thin films. Efforts of thin film preparation started soon after the discovery of Fe-based superconductors, but none of the earlier attempts had succeeded in an in-situ growth of a superconducting film of LnFeAs(O,F) (Ln=lanthanide), which exhibits the highest Tc to date among the Fe-based superconductors. Here, we report on the successful growth of NdFeAs(O,F) thin films on GaAs substrates, which showed well-defined superconducting transitions up to 48 K without the need of an ex-situ heat treatment

Ventilation and Perfusion at the Alveolar Level: Insights From Lung Intravital Microscopy

Intravital microscopy (IVM) offers unique possibilities for the observation of biological processes and disease related mechanisms in vivo. Especially for anatomically complex and dynamic organs such as the lung and its main functional unit, the alveolus, IVM provides exclusive advantages in terms of spatial and temporal resolution. By the use of lung windows, which have advanced and improved over time, direct access to the lung surface is provided. In this review we will discuss two main topics, namely alveolar dynamics and perfusion from the perspective of IVM-based studies. Of special interest are unanswered questions regarding alveolar dynamics such as: What are physiologic alveolar dynamics? How do these dynamics change under pathologic conditions and how do those changes contribute to ventilator-induced lung injury? How can alveolar dynamics be targeted in a beneficial way? With respect to alveolar perfusion IVM has propelled our understanding of the pulmonary microcirculation and its perfusion, as well as pulmonary vasoreactivity, permeability and immunological aspects. Whereas the general mechanism behind these processes are understood, we still lack a proper understanding of the complex, multidimensional interplay between alveolar ventilation and microvascular perfusion, capillary recruitment, or vascular immune responses under physiologic and pathologic conditions. These are only part of the unanswered questions and problems, which we still have to overcome. IVM as the tool of choice might allow us to answer part of these questions within the next years or decades. As every method, IVM has advantages as well as limitations, which have to be taken into account for data analysis and interpretation, which will be addressed in this review

Growth of a smooth CaF 2 layer on NdFeAsO thin film

We studied the method to grow a smooth and flat CaF 2 layer on NdFeAsO thin films since CaF 2 is a promising candidate material for the barrier layer of a superconducting junction. When the CaF 2 layer was grown at 800°C, the surface was very rough because {111} facets had grown preferentially. However, when CaF 2 was grown at lower temperatures and post-annealed in situ at 800°C for 30 min the facets were eliminated and a CaF 2 layer with a smooth surface was obtained. Fluorine diffusing from CaF 2 into NdFeAsO was observed when CaF 2 was grown at high temperatures, but the diffusion was suppressed by lowering the growth temperature to 400°C

Multiple superconducting gap and anisotropic spin fluctuations in iron arsenides: Comparison with nickel analog

We present extensive 75As NMR and NQR data on the superconducting arsenides PrFeAs0.89F0.11 (Tc=45 K), LaFeAsO0.92F0.08 (Tc=27 K), LiFeAs (Tc = 17 K) and Ba0.72K0.28Fe2As2 (Tc = 31.5 K) single crystal, and compare with the nickel analog LaNiAsO0.9F0.1 (Tc=4.0 K) . In contrast to LaNiAsO0.9F0.1 where the superconducting gap is shown to be isotropic, the spin lattice relaxation rate 1/T1 in the Fe-arsenides decreases below Tc with no coherence peak and shows a step-wise variation at low temperatures. The Knight shift decreases below Tc and shows a step-wise T variation as well. These results indicate spinsinglet superconductivity with multiple gaps in the Fe-arsenides. The Fe antiferromagnetic spin fluctuations are anisotropic and weaker compared to underdoped copper-oxides or cobalt-oxide superconductors, while there is no significant electron correlations in LaNiAsO0.9F0.1. We will discuss the implications of these results and highlight the importance of the Fermi surface topology.Comment: 6 pages, 11 figure

Triple quantum nutation in the two-level NMR system in the rotating frame

金沢大学人間社会研究域学校教育系The authors present the detailed theory and the new results associated with the triple quantum (TQ) nutation and the line narrowing effect of the TQ resonance in the two-level NMR system which we reported previously. The TQ resonance is induced in the spin-locked system by the oscillating field produced by the sinusoidal phase modulation (PM) of the RF field. The theory predicts that the TQ nutation is accompanied by several higher frequency oscillations and we detected them experimentally by improving the detection system. These higher frequency oscillations are due to the fluctuation of the angle between the transverse or effective field causing the TQ nutation and the RF field. We obtain the result that the modulation index 2φm of the PM is the key parameter that essentially controls the conditions of the TQ resonance and the narrowing effect. Under the exact TQ resonance, the ratio of the TQ resonance frequency to the Larmor frequency of the RF field depends only on φm, and the secular part of the magnetic dipole Hamiltonian of a like spin system in the triply rotating frame disappears at a particular value of φm. The condition is different from that of the well-known magic angle condition. © 2003 Elsevier Inc. All rights reserved

Analysis of interdiffusion between SmFeAsO0.92F0.08 and metals for ex situ fabrication of superconducting wire

We demonstrate the fabrication of superconducting SmFeAsO1-xFx (Sm-1111) wires by using the ex-situ powder-in-tube technique. Sm-1111 powder and a binder composed of SmF3, samarium arsenide, and iron arsenide were used to synthesize the superconducting core. Although the F content of Sm-1111 is reduced in the process of ex-situ fabrication, the binder compensates by sufficiently supplementing the F content, thereby preventing a decrease in the superconducting transition temperature and a shrinking of the superconducting volume fraction. Thus, in the superconducting Sm-1111 wire with the binder, the transport critical current density reaches the highest value of ~4000 A/cm2 at 4.2 K