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Showing papers by "Technische Universität Darmstadt published in 2008"


Journal ArticleDOI
K. Aamodt1, A. Abrahantes Quintana, R. Achenbach2, S. Acounis3  +1151 moreInstitutions (76)
TL;DR: The Large Ion Collider Experiment (ALICE) as discussed by the authors is a general-purpose, heavy-ion detector at the CERN LHC which focuses on QCD, the strong-interaction sector of the Standard Model.
Abstract: ALICE (A Large Ion Collider Experiment) is a general-purpose, heavy-ion detector at the CERN LHC which focuses on QCD, the strong-interaction sector of the Standard Model. It is designed to address the physics of strongly interacting matter and the quark-gluon plasma at extreme values of energy density and temperature in nucleus-nucleus collisions. Besides running with Pb ions, the physics programme includes collisions with lighter ions, lower energy running and dedicated proton-nucleus runs. ALICE will also take data with proton beams at the top LHC energy to collect reference data for the heavy-ion programme and to address several QCD topics for which ALICE is complementary to the other LHC detectors. The ALICE detector has been built by a collaboration including currently over 1000 physicists and engineers from 105 Institutes in 30 countries. Its overall dimensions are 161626 m3 with a total weight of approximately 10 000 t. The experiment consists of 18 different detector systems each with its own specific technology choice and design constraints, driven both by the physics requirements and the experimental conditions expected at LHC. The most stringent design constraint is to cope with the extreme particle multiplicity anticipated in central Pb-Pb collisions. The different subsystems were optimized to provide high-momentum resolution as well as excellent Particle Identification (PID) over a broad range in momentum, up to the highest multiplicities predicted for LHC. This will allow for comprehensive studies of hadrons, electrons, muons, and photons produced in the collision of heavy nuclei. Most detector systems are scheduled to be installed and ready for data taking by mid-2008 when the LHC is scheduled to start operation, with the exception of parts of the Photon Spectrometer (PHOS), Transition Radiation Detector (TRD) and Electro Magnetic Calorimeter (EMCal). These detectors will be completed for the high-luminosity ion run expected in 2010. This paper describes in detail the detector components as installed for the first data taking in the summer of 2008.

1,218 citations


Journal ArticleDOI
TL;DR: A novel method for detecting and localizing objects of a visual category in cluttered real-world scenes that is applicable to a range of different object categories, including both rigid and articulated objects and able to achieve competitive object detection performance from training sets that are between one and two orders of magnitude smaller than those used in comparable systems.
Abstract: This paper presents a novel method for detecting and localizing objects of a visual category in cluttered real-world scenes. Our approach considers object categorization and figure-ground segmentation as two interleaved processes that closely collaborate towards a common goal. As shown in our work, the tight coupling between those two processes allows them to benefit from each other and improve the combined performance. The core part of our approach is a highly flexible learned representation for object shape that can combine the information observed on different training examples in a probabilistic extension of the Generalized Hough Transform. The resulting approach can detect categorical objects in novel images and automatically infer a probabilistic segmentation from the recognition result. This segmentation is then in turn used to again improve recognition by allowing the system to focus its efforts on object pixels and to discard misleading influences from the background. Moreover, the information from where in the image a hypothesis draws its support is employed in an MDL based hypothesis verification stage to resolve ambiguities between overlapping hypotheses and factor out the effects of partial occlusion. An extensive evaluation on several large data sets shows that the proposed system is applicable to a range of different object categories, including both rigid and articulated objects. In addition, its flexible representation allows it to achieve competitive object detection performance already from training sets that are between one and two orders of magnitude smaller than those used in comparable systems.

1,084 citations


Journal ArticleDOI
TL;DR: In this article, the authors summarize progress with respect to different approaches to isolate, extract, and quantify organomineral compounds from soils, types of mineral surfaces and associated interactions, the distribution and function of soil biota at organo-mineral surfaces, and factors controlling the turnover of organic matter (OM) in organic matter associations from temperate soils.
Abstract: We summarize progress with respect to (1) different approaches to isolate, extract, and quantify organo-mineral compounds from soils, (2) types of mineral surfaces and associated interactions, (3) the distribution and function of soil biota at organo-mineral surfaces, (4) the distribution and content of organo-mineral associations, and (5) the factors controlling the turnover of organic matter (OM) in organo-mineral associations from temperate soils. Physical fractionation achieves a rough separation between plant residues and mineral-associated OM, which makes density or particle-size fractionation a useful pretreatment for further differentiation of functional fractions. A part of the OM in organo-mineral associations resists different chemical treatments, but the data obtained cannot readily be compared among each other, and more research is necessary on the processes underlying resistance to treatments for certain OM components. Studies using physical-fractionation procedures followed by soil-microbiological analyses revealed that organo-mineral associations spatially isolate C sources from soil biota, making quantity and quality of OM in microhabitats an important factor controlling community composition. The distribution and activity of soil microorganisms at organo-mineral surfaces can additionally be modified by faunal activities. Composition of OM in organo-mineral associations is highly variable, with loamy soils having generally a higher contribution of polysaccharides, whereas mineral-associated OM in sandy soils is often more aliphatic. Though highly reactive towards Fe oxide surfaces, lignin and phenolic components are usually depleted in organo-mineral associations. Charred OM associated with the mineral surface contributes to a higher aromaticity in heavy fractions. The relative proportion of OC bound in organo-mineral fractions increases with soil depth. Likewise does the strength of the bonding. Organic molecules sorbed to the mineral surfaces or precipitated by Al are effectively stabilized, indicated by reduced susceptibility towards oxidative attack, higher thermal stability, and lower bioavailability. At higher surface loading, organic C is much better bioavailable, also indicated by little 14C age. In the subsurface horizons of the soils investigated in this study, Fe oxides seem to be the most important sorbents, whereas phyllosilicate surfaces may be comparatively more important in topsoils. Specific surface area of soil minerals is not always a good predictor for C-stabilization potentials because surface coverage is discontinuous. Recalcitrance and accessibility/aggregation seem to determine the turnover dynamics in fast and intermediate cycling OM pools, but for long-term OC preservation the interactions with mineral surfaces, and especially with Fe oxide surfaces, are a major control in all soils investigated here.

928 citations


Journal ArticleDOI
TL;DR: In this paper, the authors defined severe plastic deformation (SPD) as metal forming processes in which a very large plastic strain is imposed on a bulk process in order to make an ultra-fine grained metal.
Abstract: Processes of severe plastic deformation (SPD) are defined as metal forming processes in which a very large plastic strain is imposed on a bulk process in order to make an ultra-fine grained metal The objective of the SPD processes for creating ultra-fine grained metal is to produce lightweight parts by using high strength metal for the safety and reliability of micro-parts and for environmental harmony In this keynote paper, the fabrication process of equal channel angular pressing (ECAP), accumulative roll-bonding (ARB), high pressure torsion (HPT), and others are introduced, and the properties of metals processed by the SPD processes are shown Moreover, the combined processes developed recently are also explained Finally, the applications of the ultra-fine grained (UFG) metals are discussed

849 citations


Journal ArticleDOI
TL;DR: It is shown that < or =25% of DSBs require ATM signaling for repair, and this percentage correlates with increased chromatin but not damage complexity, which suggests that the importance of ATM signalling for DSB repair increases as the heterochromatic component of a genome expands.

845 citations


Journal ArticleDOI
TL;DR: This work proposes a suitable extension of label ranking that incorporates the calibrated scenario and substantially extends the expressive power of existing approaches and suggests a conceptually novel technique for extending the common learning by pairwise comparison approach to the multilabel scenario, a setting previously not being amenable to the pairwise decomposition technique.
Abstract: Label ranking studies the problem of learning a mapping from instances to rankings over a predefined set of labels. Hitherto existing approaches to label ranking implicitly operate on an underlying (utility) scale which is not calibrated in the sense that it lacks a natural zero point. We propose a suitable extension of label ranking that incorporates the calibrated scenario and substantially extends the expressive power of these approaches. In particular, our extension suggests a conceptually novel technique for extending the common learning by pairwise comparison approach to the multilabel scenario, a setting previously not being amenable to the pairwise decomposition technique. The key idea of the approach is to introduce an artificial calibration label that, in each example, separates the relevant from the irrelevant labels. We show that this technique can be viewed as a combination of pairwise preference learning and the conventional relevance classification technique, where a separate classifier is trained to predict whether a label is relevant or not. Empirical results in the area of text categorization, image classification and gene analysis underscore the merits of the calibrated model in comparison to state-of-the-art multilabel learning methods.

825 citations


Journal ArticleDOI
TL;DR: This work shows that a simple (weighted) voting strategy minimizes risk with respect to the well-known Spearman rank correlation and compares RPC to existing label ranking methods, which are based on scoring individual labels instead of comparing pairs of labels.

538 citations


Journal ArticleDOI
TL;DR: In this paper, the authors applied bulk and surface sensitive x-ray spectroscopic techniques to show that the valence band edge for In2O3 is significantly closer to the bottom of the conduction band than expected on the basis of the widely quoted bulk band gap of 3.75 eV.
Abstract: Bulk and surface sensitive x-ray spectroscopic techniques are applied in tandem to show that the valence band edge for In2O3 is found significantly closer to the bottom of the conduction band than expected on the basis of the widely quoted bulk band gap of 3.75 eV. First-principles theory shows that the upper valence bands of In2O3 exhibit a small dispersion and the conduction band minimum is positioned at Gamma. However, direct optical transitions give a minimal dipole intensity until 0.8 eV below the valence band maximum. The results set an upper limit on the fundamental band gap of 2.9 eV.

523 citations


Proceedings ArticleDOI
21 Sep 2008
TL;DR: Experimental results show the ability of the approach to model and recognize daily routines without user annotation to be able to be used in this work.
Abstract: In this work we propose a novel method to recognize daily routines as a probabilistic combination of activity patterns. The use of topic models enables the automatic discovery of such patterns in a user's daily routine. We report experimental results that show the ability of the approach to model and recognize daily routines without user annotation.

473 citations


Journal ArticleDOI
TL;DR: In this paper, Jin et al. considered purely stress-driven interactions between 60° non-screw lattice dislocation and coherent twin boundary (CTB) via molecular dynamics simulations for three face-centered cubic (fcc) metals, Cu, Ni and Al.

467 citations



Journal ArticleDOI
TL;DR: Heterologous genes encoding biosynthetic enzymes from the early part of the taxoid biosynthesis pathway, isoprenoid pathway, as well as a regulatory factor to inhibit competitive pathways are introduced and their impact on taxadiene synthesis is studied.

Journal ArticleDOI
TL;DR: The existing theoretical work on AIS is reviewed and details of the theoretical analysis for each of the three main types of AIS algorithm, clonal selection, immune network and negative selection, are given.

Journal ArticleDOI
TL;DR: This work shows that the tobacco (Nicotiana tabacum) plasma membrane and inner chloroplast membranes contain the aquaporin Nt AQP1, which opens new opportunities for mechanistic examination of leaf internal CO2 conductance regulation.
Abstract: Photosynthesis is often limited by the rate of CO2 diffusion from the atmosphere to the chloroplast. The primary resistances for CO2 diffusion are thought to be at the stomata and at photosynthesizing cells via a combination resulting from resistances of aqueous solution as well as the plasma membrane and both outer and inner chloroplast membranes. In contrast with stomatal resistance, the resistance of biological membranes to gas transport is not widely recognized as a limiting factor for metabolic function. We show that the tobacco (Nicotiana tabacum) plasma membrane and inner chloroplast membranes contain the aquaporin Nt AQP1. RNA interference–mediated decreases in Nt AQP1 expression lowered the CO2 permeability of the inner chloroplast membrane. In vivo data show that the reduced amount of Nt AQP1 caused a 20% change in CO2 conductance within leaves. Our discovery of CO2 aquaporin function in the chloroplast membrane opens new opportunities for mechanistic examination of leaf internal CO2 conductance regulation.

Journal ArticleDOI
TL;DR: A major advantage of the developed evaporation model is that it does not refer to intrinsic details of the interface-capturing scheme, but relies on continuum-field quantities that can be computed by virtually any CFD approach.

Journal ArticleDOI
12 Jun 2008-Nature
TL;DR: Findings indicate that substrate targeting by GSMs mechanistically links two therapeutic actions: alteration in Aβ42 production and inhibition of amyloid-β aggregation, which may synergistically reduce amyloids-β deposition in Alzheimer’s disease.
Abstract: Selective lowering of Abeta42 levels (the 42-residue isoform of the amyloid-beta peptide) with small-molecule gamma-secretase modulators (GSMs), such as some non-steroidal anti-inflammatory drugs, is a promising therapeutic approach for Alzheimer's disease. To identify the target of these agents we developed biotinylated photoactivatable GSMs. GSM photoprobes did not label the core proteins of the gamma-secretase complex, but instead labelled the beta-amyloid precursor protein (APP), APP carboxy-terminal fragments and amyloid-beta peptide in human neuroglioma H4 cells. Substrate labelling was competed by other GSMs, and labelling of an APP gamma-secretase substrate was more efficient than a Notch substrate. GSM interaction was localized to residues 28-36 of amyloid-beta, a region critical for aggregation. We also demonstrate that compounds known to interact with this region of amyloid-beta act as GSMs, and some GSMs alter the production of cell-derived amyloid-beta oligomers. Furthermore, mutation of the GSM binding site in the APP alters the sensitivity of the substrate to GSMs. These findings indicate that substrate targeting by GSMs mechanistically links two therapeutic actions: alteration in Abeta42 production and inhibition of amyloid-beta aggregation, which may synergistically reduce amyloid-beta deposition in Alzheimer's disease. These data also demonstrate the existence and feasibility of 'substrate targeting' by small-molecule effectors of proteolytic enzymes, which if generally applicable may significantly broaden the current notion of 'druggable' targets.

Journal ArticleDOI
TL;DR: In this paper, the properties of ghost and gluon propagators in the deep infrared momentum region of Landau gauge Yang-Mills theory were discussed. And it was shown that it is only a matter of infrared boundary conditions whether infrared scaling or decoupling occurs.
Abstract: We discuss the properties of ghost and gluon propagators in the deep infrared momentum region of Landau gauge Yang-Mills theory. Within the framework of Dyson-Schwinger equations and the functional renormalization group we demonstrate that it is only a matter of infrared boundary conditions whether infrared scaling or decoupling occurs. We argue that the second possibility is at odds with global BRST symmetry in the confining phase. For this purpose we improve upon existing truncation schemes in particular with respect to transversality and renormalization.

Book ChapterDOI
12 Oct 2008
TL;DR: The ground truth enables us to model how the assumption of brightness constancy is violated in naturalistic sequences, resulting in a probabilistic model of "brightness inconstancy", and generalize previous high- order constancy assumptions by modeling the constancy of responses to various linear filters in a high-order random field framework.
Abstract: Assumptions of brightness constancy and spatial smoothness underlie most optical flow estimation methods. In contrast to standard heuristic formulations, we learn a statistical model of both brightness constancy error and the spatial properties of optical flow using image sequences with associated ground truth flow fields. The result is a complete probabilistic model of optical flow. Specifically, the ground truth enables us to model how the assumption of brightness constancy is violated in naturalistic sequences, resulting in a probabilistic model of "brightness inconstancy". We also generalize previous high-order constancy assumptions, such as gradient constancy, by modeling the constancy of responses to various linear filters in a high-order random field framework. These filters are free variables that can be learned from training data. Additionally we study the spatial structure of the optical flow and how motion boundaries are related to image intensity boundaries. Spatial smoothness is modeled using a Steerable Random Field, where spatial derivatives of the optical flow are steered by the image brightness structure. These models provide a statistical motivation for previous methods and enable the learning of all parameters from training data. All proposed models are quantitatively compared on the Middlebury flow dataset.

Journal ArticleDOI
TL;DR: A facile strategy based on the use of bifunctional macromolecular ligands to electrostatically assemble biorecongnition sites into the nanochannel wall, which can then be used as recognition elements for constructing a nanobiosensor and it is demonstrated that this approach enables the creation of supramolecular multilayered structures inside the nanopore that are stabilized by strong ligand-receptor interactions.
Abstract: There is a growing quest for tailorable nanochannels or nanopores having dimensions comparable to the size of biological molecules and mimicking the function of biological ion channels. This interest is based on the use of nanochannels as extremely sensitive single molecule biosensors. The biosensing capabilities of these nanochannels depend sensitively on the surface characteristics of their inner walls to achieve the desired functionality of the biomimetic system. Nanoscale control over the surface properties of the nanochannel plays a crucial role in the biosensing performance due to the chemical groups incorporated on the inner channel walls that act as binding sites for different analytes and interact with molecules passing through the channel. Here we report a new approach to incorporate biosensing elements into polymer nanochannels by using electrostatic self-assembly. We describe a facile strategy based on the use of bifunctional macromolecular ligands to electrostatically assemble biorecongnition sites into the nanochannel wall, which can then be used as recognition elements for constructing a nanobiosensor. The experimental results demonstrate that the ligand-functionalized nanochannels are very stable and the biorecognition event (protein conjugation) does not promote the removal of the ligands from the channel surface. In addition, control experiments indicated that the electrostatically assembled nanochannel surface displays good biospecificity and nonfouling properties. Then, we demonstrate that this approach also enables the creation of supramolecular multilayered structures inside the nanopore that are stabilized by strong ligand-receptor interactions. We envision that the formation of multilayered supramolecular assemblies inside solid-state nanochannels will play a key role in the further expansion of the toolbox called "soft nanotechnology", as well as in the construction of new multifunctional biomimetic systems.

Journal ArticleDOI
TL;DR: Emphasis is placed on certain aspects of water stress reactions and the correlation of aquaporins to abscisic acid as well as on the relation of water and CO2 permeability in leaves.
Abstract: The impact of aquaporin function on plant water balance is discussed. The significance of these proteins for root water uptake, water conductance in the xylem, including embolism refilling and the role of plant aquaporins in leaf physiology, is described. Emphasis is placed on certain aspects of water stress reactions and the correlation of aquaporins to abscisic acid as well as on the relation of water and CO2 permeability in leaves.

Book ChapterDOI
10 Jun 2008
TL;DR: A systematic comparison of the most prominent and successful people detectors is contributed and a new detector is proposed that outperforms the state-of-art on the INRIA person dataset by combining multiple features.
Abstract: Over the years a number of powerful people detectors have been proposed. While it is standard to test complete detectors on publicly available datasets, it is often unclear how the different components (e.g. features and classifiers) of the respective detectors compare. Therefore, this paper contributes a systematic comparison of the most prominent and successful people detectors. Based on this evaluation we also propose a new detector that outperforms the state-of-art on the INRIA person dataset by combining multiple features.


Journal ArticleDOI
Néstor Armesto1, Nicolas Borghini2, Sangyong Jeon3, Urs Achim Wiedemann4  +191 moreInstitutions (63)
TL;DR: A compilation of predictions for the forthcoming Heavy Ion Program at the Large Hadron Collider, as presented at the CERN Theory Institute 'Heavy Ion Collisions at the LHC - Last Call for Predictions', held from 14th May to 10th June 2007, can be found in this article.
Abstract: This writeup is a compilation of the predictions for the forthcoming Heavy Ion Program at the Large Hadron Collider, as presented at the CERN Theory Institute 'Heavy Ion Collisions at the LHC - Last Call for Predictions', held from 14th May to 10th June 2007.

Journal ArticleDOI
TL;DR: Strongly correlated systems far from equilibrium can exhibit scaling solutions with a dynamically generated weak coupling by investigating isolated systems described by relativistic quantum field theories for initial conditions leading to nonequilibrium instabilities, such as parametric resonance or spinodal decomposition.
Abstract: Strongly correlated systems far from equilibrium can exhibit scaling solutions with a dynamically generated weak coupling. We show this by investigating isolated systems described by relativistic quantum field theories for initial conditions leading to nonequilibrium instabilities, such as parametric resonance or spinodal decomposition. The nonthermal fixed points prevent fast thermalization if classical-statistical fluctuations dominate over quantum fluctuations. We comment on the possible significance of these results for the heating of the early Universe after inflation and the question of fast thermalization in heavy-ion collision experiments.

Journal ArticleDOI
TL;DR: In this article, coarse-grained potentials of polystyrene and ethylbenzene were optimized against the fully atomistic simulations until the radial distribution functions generated from coarsegrained simulations are consistent with atomistic simulation.
Abstract: In this article, we present coarse-grained potentials of ethylbenzene developed at 298 K and of amorphous polystyrene developed at 500 K by the pressure-corrected iterative Boltzmann inversion method. The potentials are optimized against the fully atomistic simulations until the radial distribution functions generated from coarse-grained simulations are consistent with atomistic simulations. In the coarse-grained polystyrene melts of different chain lengths, the Flory exponent of 0.58 is obtained for chain statistics. Both potentials of polystyrene and ethylbenzene are transferable over a broad range of temperature. The thermal expansion coefficients of the fully atomistic simulations are well reproduced in the coarse-grained models for both systems. However, for the case of ethylbenzene, the coarse-grained potential is temperature-dependent. The potential needs to be modified by a temperature factor of T/T0 when it is transferred to other temperatures; T0 = 298 K is the temperature at which the coarse-gr...

Journal ArticleDOI
TL;DR: There is a significant mismatch between the “two level” modeling paradigm used to construct mainstream domain models and the conceptual information such models are required to represent—a mismatch that makes such models more complex than they need be.
Abstract: A fundamental principle in engineering, including software engineering, is to minimize the amount of accidental complexity which is introduced into engineering solutions due to mismatches between a problem and the technology used to represent the problem. As model-driven development moves to the center stage of software engineering, it is particularly important that this principle be applied to the technologies used to create and manipulate models, especially models that are intended to be free of solution decisions. At present, however, there is a significant mismatch between the “two level” modeling paradigm used to construct mainstream domain models and the conceptual information such models are required to represent—a mismatch that makes such models more complex than they need be. In this paper, we identify the precise nature of the mismatch, discuss a number of more or less satisfactory workarounds, and show how it can be avoided.

Journal ArticleDOI
TL;DR: A detailed study of the transferability over different thermodynamic states of a coarse-grained (CG) force field developed using the iterative Boltzmann inversion method and finds that the polymer chain length does not affect the transferable of the force field and is attributed mainly to the finer model used in describing the polyamide-6,6 than the polystyrene.
Abstract: A key question for all coarse-graining methodologies is the degree of transferability of the resulting force field between various systems and thermodynamic conditions. Here we present a detailed study of the transferability over different thermodynamic states of a coarse-grained (CG) force field developed using the iterative Boltzmann inversion method. The force field is optimized against distribution functions obtained from atomistic simulations. We analyze the polymer case by investigating the bulk of polystyrene and polyamide-6,6 whose coarse-grained models differ in the chain length and in the number of atoms lumped in one bead. The effect of temperature and pressure on static, dynamic, and thermodynamic properties is tested by comparing systematically the coarse-grain results with the atomistic ones. We find that the CG model describing the polystyrene is transferable only in a narrow range of temperature and it fails in describing the change of the bulk density when temperature is 80 K lower than the optimization one. Moreover the calculation of the self-diffusion coefficient shows that the CG model is characterized by a faster dynamics than the atomistic one and that it overestimates the isothermal compressibility. On the contrary, the polyamide-6,6 CG model turns out to be fully transferable between different thermodynamic conditions. The transferability is checked by changing either the temperature or the pressure of the simulation. We find that, in this case, the CG model is able to follow all the intra- and interstructural rearrangements caused by the temperature changes. In addition, while at low temperature the difference between the CG and atomistic dynamics is remarkable due to the presence of hydrogen bonds in the atomistic systems, for high temperatures, the speedup of the CG dynamics is strongly reduced, leading to a CG diffusion coefficient only six times bigger than the atomistic one. Moreover, the isothermal compressibility calculated at different temperatures agrees very well with the experimental one. We find that the polymer chain length does not affect the transferability of the force field and we attribute such transferability mainly to the finer model used in describing the polyamide-6,6 than the polystyrene.

Book ChapterDOI
17 Aug 2008
TL;DR: In this article, the authors strengthen the foundations of deterministic public-key encryption via definitional equivalences and standard-model constructs based on general assumptions, and show relations between deterministic and standard (randomized) encryption.
Abstract: We strengthen the foundations of deterministic public-key encryption via definitional equivalences and standard-model constructs based on general assumptions. Specifically we consider seven notions of privacy for deterministic encryption, including six forms of semantic security and an indistinguishability notion, and show them all equivalent. We then present a deterministic scheme for the secure encryption of uniformly and independently distributed messages based solely on the existence of trapdoor one-way permutations. We show a generalization of the construction that allows secure deterministic encryption of independent high-entropy messages. Finally we show relations between deterministic and standard (randomized) encryption.

Journal ArticleDOI
TL;DR: Targeting of AKT enhances radiation sensitivity of lung cancer cell lines A549 and H460 most likely through specific inhibition of DNA-PKcs-dependent DNA-dsb repair but not through enhancement of radiation-induced apoptosis.
Abstract: We have already reported that epidermal growth factor receptor/phosphatidylinositol 3-kinase/AKT signaling is an important pathway in regulating radiation sensitivity and DNA double-strand break (DNA-dsb) repair of human tumor cells. In the present study, we investigated the effect of AKT1 on DNA-dependent protein kinase catalytic subunit (DNA-PKcs) activity and DNA-dsb repair in irradiated non-small cell lung cancer cell lines A549 and H460. Treatment of cells with the specific AKT pathway inhibitor API-59 CJ-OH (API; 1-5 micromol/L) reduced clonogenic survival between 40% and 85% and enhanced radiation sensitivity of both cell lines significantly. As indicated by fluorescence-activated cell sorting analysis (sub-G(1) cells) and poly(ADP-ribose) polymerase cleavage, API treatment or transfection with AKT1-small interfering RNA (siRNA) induced apoptosis of H460 but not of A549 cells. However, in either apoptosis-resistant A549 or apoptosis-sensitive H460 cells, API and/or AKT1-siRNA did not enhance poly(ADP-ribose) polymerase cleavage and apoptosis following irradiation. Pretreatment of cells with API or transfection with AKT1-siRNA strongly inhibited radiation-induced phosphorylation of DNA-PKcs at T2609 and S2056 as well as repair of DNA-dsb as measured by the gamma-H2AX foci assay. Coimmunoprecipitation experiments showed a complex formation of activated AKT and DNA-PKcs, supporting the assumption that AKT plays an important regulatory role in the activation of DNA-PKcs in irradiated cells. Thus, targeting of AKT enhances radiation sensitivity of lung cancer cell lines A549 and H460 most likely through specific inhibition of DNA-PKcs-dependent DNA-dsb repair but not through enhancement of radiation-induced apoptosis.

Journal ArticleDOI
TL;DR: In this paper, a short overview on how to introduce the anisotropic environment necessary to measure residual dipolar couplings, the corresponding measurement methods and the applications for the determination of the relative configurations and the assignment of diastereotopic moieties is presented.