Bioinformatics

Motivation: Chromatin immunoprecipitation (ChIP) is a powerful experimental approach to identify in vivo binding sites of sequence-specific transcription factors (TFs). These experiments are designed to specifically enrich DNA fragments that are bound to the TF. Tiling arrays have become more and more popular for the identification of these DNA fragments. However, many studies showed that only a fraction of the identified DNA fragments contains bona fide binding sites for the TF, suggesting that indirect binding mechanisms play a very important role. We explored the possibility that the lack of binding sites can also be explained by problems in identifying ChIP-enriched DNA fragments from the measured intensities. Results: We derived a physical model that explains some (but not all) variation of the measured probe intensities of Affymetrix tilling arrays. We used the physical model to estimate the probe-specific behavior and corrected for it. Subsequently, we developed a method to identify ChIP-enriched DNA fragments. We termed it physical model for tiling array analysis (PMT). We applied PMT to the data of ChIP-chip experiments interrogating chromosome 21 and 22 of the human genome for binding of the TFs MYC, SP1 and P53. Almost all regions recovered by PMT showed evidence for sequence-specific binding of the TFs

Influence of composition and precipitation evolution on damage at grain boundaries in a crept polycrystalline Ni-based superalloy

© 2018 Acta Materialia Inc. The microstructural and compositional evolution of intergranular carbides and borides prior to and after creep deformation at 850 °C in a polycrystalline nickel-based superalloy was studied. Primary MC carbides, enveloped within intergranular γ′ layers, decomposed resulting in the formation of layers of the undesirable η phase. These layers have a composition corresponding to Ni3Ta as measured by atom probe tomography and their structure is consistent with the D024 hexagonal structure as revealed by transmission electron microscopy. Electron backscattered diffraction reveals that they assume various misorientations with regard to the adjacent grains. As a consequence, these layers act as brittle recrystallized zones and crack initiation sites. The composition of the MC carbides after creep was altered substantially, with the Ta content decreasing and the Hf and Zr contents increasing, suggesting a beneficial effect of Hf and Zr additions on the stability of MC carbides. By contrast, M5B3 borides were found to be microstructurally stable after creep and without substantial compositional changes. Borides at 850 °C were found to coarsen, resulting in some cases into γ′- depleted zones, where, however, no cracks were observed. The major consequences of secondary phases on the microstructural stability of superalloys during the design of new polycrystalline superalloys are discussed

Stellar Wind Accretion in GX301-2: Evidence for a High-density Stream

The X-ray binary system GX301-2 consists of a neutron star in an eccentric orbit accreting from the massive early-type star WRAY 977. It has previously been shown that the X-ray orbital light curve is consistent with existence of a gas stream flowing out from Wray 977 in addition to its strong stellar wind. Here, X-ray monitoring observations by the Rossi X-ray Timing Explorer (RXTE)/ All-Sky-Monitor (ASM) and pointed observations by the RXTE/ Proportional Counter Array (PCA) over the past decade are analyzed. We analyze both the flux and column density dependence on orbital phase. The wind and stream dynamics are calculated for various system inclinations, companion rotation rates and wind velocities, as well as parametrized by the stream width and density. These calculations are used as inputs to determine both the expected accretion luminosity and the column density along the line-of-sight to the neutron star. The model luminosity and column density are compared to observed flux and column density vs. orbital phase, to constrain the properties of the stellar wind and the gas stream. We find that the change between bright and medium intensity levels is primarily due to decreased mass loss in the stellar wind, but the change between medium and dim intensity levels is primarily due to decreased stream density. The mass-loss rate in the stream exceeds that in the stellar wind by a factor of 2.5. The quality of the model fits is significantly better for lower inclinations, favoring a mass for WRAY 977 of 53 to 62 Msun.Comment: 19 pages, 6 figure

Decomposition of fractional quantum Hall states: New symmetries and approximations

We provide a detailed description of a new symmetry structure of the monomial (Slater) expansion coefficients of bosonic (fermionic) fractional quantum Hall states first obtained in Ref. 1, which we now extend to spin-singlet states. We show that the Haldane-Rezayi spin-singlet state can be obtained without exact diagonalization through a differential equation method that we conjecture to be generic to other FQH model states. The symmetry rules in Ref. 1 as well as the ones we obtain for the spin singlet states allow us to build approximations of FQH states that exhibit increasing overlap with the exact state (as a function of system size). We show that these overlaps reach unity in the thermodynamic limit even though our approximation omits more than half of the Hilbert space. We show that the product rule is valid for any FQH state which can be written as an expectation value of parafermionic operators.Comment: 22 pages, 8 figure

Effect of off-stoichiometric compositions on microstructures and phase transformation behavior in Ni-Cu-Pd-Ti-Zr-Hf high entropy shape memory alloys

High entropy shape memory alloys (HE-SMAs) show reversible martensitic phase transformations at elevated temperatures. HE-SMAs were derived from binary NiTi, to which the elements Cu, Pd, Zr and Hf are added. They represent ordered complex solid solutions. Their high temperature phase is of B2 type, where the added elements occupy sites in the Ni-(Cu, Pd) and Ti-sub-lattices (Zr, Hf). In the present study, advanced microstructural and thermal characterization methods were used to study the effects of the additional alloy elements on microstructures and phase transformations. The ratios of Ni-equivalent (Ni, Cu, Pd) and Ti-equivalent (Ti, Zr, Hf) elements in HE-SMAs were varied to establish systems that correspond to stoichiometric, under- and over-stoichiometric binary alloys. It is shown that basic microstructural features of cast and heat-treated HE-SMAs are inherited from the nine binary X–Y subsystems (X: Ni, Cu, Pd; Y: Ti, Zr, Hf). The phase transition temperatures that characterize the martensitic forward and reverse transformations depend on the concentrations of all alloy elements. The data obtained demonstrate how martensite start temperatures are affected by deviations from the composition of an ideal stoichiometric B2 phase. The findings are discussed in the light of previous work on the concentration dependence of SMA transformation temperatures, and directions for the development of new shape memory alloy compositions are proposed. © 2020 The Author

Two different subunits of importin cooperate to recognize nuclear localization signals and bind them to the nuclear envelope

AbstractBackground: Selective protein import into the cell nucleus occurs in two steps: binding to the nuclear envelope, followed by energy-dependent transit through the nuclear pore complex. A 60 kD protein, importin, is essential for the first nuclear import step, and the small G protein Ran/TC4 is essential for the second. We have previously purified the 60 kD importin protein (importin 60) as a single polypeptide.Results We have identified importin 90, a 90 kD second subunit that dissociates from importin 60 during affinity chromatography on nickel (II)–nitrolotriacetic acid–Sepharose, a technique that was originally used to purify importin 60. Partial amino-acid sequencing of Xenopus importin 90 allowed us to clone and sequence its human homologue; the amino-acid sequence of importin 90 is strikingly conserved between the two species. We have also identified a homologous budding yeast sequence from a database entry. Importin 90 potentiates the effects of importin 60 on nuclear protein import, indicating that the importin complex is the physiological unit responsible for import. To assess whether nuclear localization sequences are recognized by cytosolic receptor proteins, a biotin-tagged conjugate of nuclear localization signals linked to bovine serum albumin was allowed to form complexes with cytosolic proteins in Xenopus egg extracts; the complexes were then retrieved with streptavidin–agarose. The pattern of bound proteins was surprisingly simple and showed only two predominant bands: those of the importin complex. We also expressed the human homologue of importin 60, Rch1p, and found that it was able to replace its Xenopus counterpart in a functional assay. We discuss the relationship of importin 60 and importin 90 to other nuclear import factors.Conclusion Importin consists of a 60 and a 90 kD subunit. Together, they constitute a cytosolic receptor for nuclear localization signals that enables import substrates to bind to the nuclear envelope

Generation of x-ray radiation in a storage ring by a superconductive cold-bore invacuum undulator

The first beam measurements with a cold-bore superconducting in-vacuum undulator in a storage ring are reported. Undulators are x-ray generators in light sources. The physical limitations of these devices limit the intensity and the brilliance of the x-ray beam. At present the undulators are made from permanent magnets. It was shown in earlier papers that at low electron beam intensities superconductive wires in the vacuum beam pipe can overcome the limitations inherent to permanent magnet undulators. It was argued that the use of these novel devices in light sources with high beam currents may be limited by the extreme anomalous skin effect regime in Cu at 4.2 K, which has so far undergone very little investigation, and the power deposited by the infrared part of the synchrotron radiation. The purpose of this paper is to present measurements of these effects at the synchrotron light source ANKA with stored currents up to 200 mA

Shared Governance in an Adult Education Doctoral Program: “Self-Directed Learning meets Democratic Process” – A Delicate Balance of Intent, Implementation, and Impact

This symposium explores the governance component offered within a doctoral program in which students were given the opportunity to engage in collective decision-making through democratic process. Panelists, most of whom were research participants for the dissertation upon which this exploration is based, represent cohort groups from 1996 through 2007