DNA damage-induced transcription stress : a focus on RNA polymerase II

The integrity of DNA is continuously challenged by genotoxic insults from both endogenous and exogenous origin. Damaged DNA disrupts essential cellular functions such as replication and transcription, and can lead to mutagenesis, senescence, and apoptosis. If unrepaired, these DNA lesion may ultimately contribute to aging, or cause mutations that may give rise to cancer. To counteract these deleterious consequences, cells are equipped with an intricate network of highly regulated processes that orchestrate the recognition and dedicated repair of DNA lesions and the activation of DNA damage-induced cell signaling pathways. In this thesis we investigated the cellular consequences of DNA-damage induced transcription stress, with a special focus on the regulation of RNA polymerase II function after UV irradiation

The growth of decagonal Al-Co-Ni single crystals as a function of chemical composition

Decaprismatic single crystals taken from a series of alloys of nominal compositions within Al65-77Co3-22Ni3-22 have been studied by means of x-ray diffraction techniques. The substitution of Co by Ni in increasing amounts changes the (pseudo)decagonal diffraction patterns drastically and indicates structural changes which range from a single-crystalline approximant via orientationally ordered nanodomain structures and quasiperiodic phases with different types of ordering phenomena, to a basic decagonal phase. A quantum phase diagram analysis shows a clear separation of the stability regions of the ternary systems described in this study and other decagonal phase

The power of sum-of-squares for detecting hidden structures

We study planted problems---finding hidden structures in random noisy inputs---through the lens of the sum-of-squares semidefinite programming hierarchy (SoS). This family of powerful semidefinite programs has recently yielded many new algorithms for planted problems, often achieving the best known polynomial-time guarantees in terms of accuracy of recovered solutions and robustness to noise. One theme in recent work is the design of spectral algorithms which match the guarantees of SoS algorithms for planted problems. Classical spectral algorithms are often unable to accomplish this: the twist in these new spectral algorithms is the use of spectral structure of matrices whose entries are low-degree polynomials of the input variables. We prove that for a wide class of planted problems, including refuting random constraint satisfaction problems, tensor and sparse PCA, densest-k-subgraph, community detection in stochastic block models, planted clique, and others, eigenvalues of degree-d matrix polynomials are as powerful as SoS semidefinite programs of roughly degree d. For such problems it is therefore always possible to match the guarantees of SoS without solving a large semidefinite program. Using related ideas on SoS algorithms and low-degree matrix polynomials (and inspired by recent work on SoS and the planted clique problem by Barak et al.), we prove new nearly-tight SoS lower bounds for the tensor and sparse principal component analysis problems. Our lower bounds for sparse principal component analysis are the first to suggest that going beyond existing algorithms for this problem may require sub-exponential time

Systematic quantitative overviews of the literature to determine the value of diagnostic tests for predicting acute appendicitis: study protocol

BACKGROUND: Suspected acute appendicitis is the most frequent cause for emergency operations in visceral surgery worldwide. In approximately twenty percent of all cases however, the diagnosis is incorrect and patients undergo surgery without having acute appendicitis. Operations of bland appendices put patients at risk and entail a serious waste of resources. Several highly accurate tests have been introduced to diagnose acute appendicitis. The false positive rate however, has not changed over the last twenty years. Given the variation that exists in both practice and research, the uncertainty regarding the quality of the underlying evidence, there is a clear need for comprehensive, systematic and quantitative overviews of the diagnostic value of the various tests purported to be predictive of acute appendicitis. METHODS: Literature will be identified searching general bibliographic databases (MEDLINE and EMBASE), specialist computer databases (DARE, Cochrane Database of Systematic Reviews, conference proceedings, MEDION, SCISEARCH, BIOSIS) without language restrictions. We will contact experts and the manufacturers of tests. Hand-searching will complete our searches. Identified articles will be selected according to populations, tests, outcomes and study design. Papers meeting the selection criteria will be appraised to rate their methodological quality. Analysis will include exploration of heterogeneity in results. We will conduct meta-analyses to generate summary estimates of test accuracy measures and summary ROC curves where appropriate. If meta-analysis is considered to be inappropriate, we will describe the identified evidence in the context of appraised quality. DISCUSSION: These reviews should lead to formulation of recommendations for current practice and future research

Interleukin-6 potentiates endurance training adaptation and improves functional capacity in old mice

Interventions to preserve functional capacities at advanced age are becoming increasingly important. So far, exercise provides the only means to counteract age-related decrements in physical performance and muscle function. Unfortunately, the effectiveness of exercise interventions in elderly populations is hampered by reduced acceptance and compliance as well as disuse complications. We therefore studied whether application of interleukin-6 (IL-6), a pleiotropic myokine that is induced by skeletal muscle activity and exerts broad systemic effects in response to exercise, affects physical performance and muscle function alone or in combination with training in aged mice.; Sedentary old male mice (Sed+Saline, n = 15) were compared with animals that received recombinant IL-6 (rIL-6) in an exercise-mimicking pulsatile manner (Sed+IL-6, n = 16), were trained with a moderate-intensity, low-volume endurance exercise regimen (Ex+Saline, n = 13), or were exposed to a combination of these two interventions (Ex+IL-6, n = 16) for 12 weeks. Before and at the end of the intervention, mice underwent a battery of tests to quantify endurance performance, muscle contractility in situ, motor coordination, and gait and metabolic parameters.; Mice exposed to enhanced levels of IL-6 during endurance exercise bouts showed superior improvements in endurance performance (33% more work and 12% greater peak power compared with baseline), fatigue resistance in situ (P = 0.0014 vs. Sed+Saline; P = 0.0199 vs. Sed+IL-6; and P = 0.0342 vs. Ex+Saline), motor coordination (rotarod performance, P = 0.0428), and gait (gait speed, P = 0.0053) following training. Pulsatile rIL-6 treatment in sedentary mice had only marginal effects on glucose tolerance and some gait parameters. No increase in adverse events or mortality related to rIL-6 treatment was observed.; Administration of rIL-6 paired with treadmill running bouts potentiates the adaptive response to a moderate-intensity low-volume endurance exercise regimen in old mice, while being safe and well tolerated

Second harmonic generation on incommensurate structures: The case of multiferroic MnWO4

A comprehensive analysis of optical second harmonic generation (SHG) on an incommensurate (IC) magnetically ordered state is presented using multiferroic MnWO4 as model compound. Two fundamentally different SHG contributions coupling to the primary IC magnetic order or to secondary commensurate projections of the IC state, respectively, are distinguished. Whereas the latter can be described within the formalism of the 122 commensurate magnetic point groups the former involves a breakdown of the conventional macroscopic symmetry analysis because of its sensitivity to the lower symmetry of the local environment in a crystal lattice. Our analysis thus foreshadows the fusion of the hitherto disjunct fields of nonlinear optics and IC order in condensed-matter systems

The local atomic quasicrystal structure of the icosahedral Mg25Y11Zn64 alloy

A local and medium range atomic structure model for the face centred icosahedral (fci) Mg25Y11Zn64 alloy has been established in a sphere of r = 27 A. The model was refined by least squares techniques using the atomic pair distribution (PDF) function obtained from synchrotron powder diffraction. Three hierarchies of the atomic arrangement can be found: (i) five types of local coordination polyhedra for the single atoms, four of which are of Frank-Kasper type. In turn, they (ii) form a three-shell (Bergman) cluster containing 104 atoms, which is condensed sharing its outer shell with its neighbouring clusters and (iii) a cluster connecting scheme corresponding to a three-dimensional tiling leaving space for few glue atoms. Inside adjacent clusters, Y8-cubes are tilted with respect to each other and thus allow for overall icosahedral symmetry. It is shown that the title compound is essentially isomorphic to its holmium analogue. Therefore fci-Mg-Y-Zn can be seen as the representative structure type for the other rare earth analogues fci-Mg-Zn-RE (RE = Dy, Er, Ho, Tb) reported in the literature.Comment: 12 pages, 8 figures, 2 table

Overlapping Unit Cells in 3d Quasicrystal Structure

A 3-dimensional quasiperiodic lattice, with overlapping unit cells and periodic in one direction, is constructed using grid and projection methods pioneered by de Bruijn. Each unit cell consists of 26 points, of which 22 are the vertices of a convex polytope P, and 4 are interior points also shared with other neighboring unit cells. Using Kronecker's theorem the frequencies of all possible types of overlapping are found.Comment: LaTeX2e, 11 pages, 5 figures (8 eps files), uses iopart.class. Final versio