The XPF-ERCC1 endonuclease and homologous recombination contribute to the repair of minor groove DNA interstrand crosslinks inmammalian cells produced by the pyrrolo[2,1-c][1,4]benzodiazepine dimer SJG-136

SJG-136, a pyrrolo[2,1-c][1,4]benzodiazepine (PBD) dimer, is a highly efficient interstrand crosslinking agent that reacts with guanine bases in a 5'-GATC-3' sequence in the DNA minor groove. SJG-136 crosslinks form rapidly and persist compared to those produced by conventional crosslinking agents such as nitrogen mustard, melphalan or cisplatin which bind in the DNA major groove. A panel of Chinese hamster ovary (CHO) cells with defined defects in specific DNA repair pathways were exposed to the bi-functional agents SJG-136 and melphalan, and to their mono-functional analogues mmy-SJG and mono-functional melphalan. SJG-136 was >100 times more cytotoxic than melphalan, and the bi-functional agents were much more cytotoxic than their respective mono-functional analogues. Cellular sensitivity of both SJG-136 and melphalan was dependent on the XPF-ERCC1 heterodimer, and homologous recombination repair factors XRCC2 and XRCC3. The relative level of sensitivity of these repair mutant cell lines to SJG-136 was, however, significantly less than with major groove crosslinking agents. In contrast to melphalan, there was no clear correlation between sensitivity to SJG-136 and crosslink unhooking capacity measured using a modified comet assay. Furthermore, repair of SJG-136 crosslinks did not involve the formation of DNA double-strand breaks. SJG-136 cytotoxicity is likely to result from the poor recognition of DNA damage by repair proteins resulting in the slow repair of both mono-adducts and more importantly crosslinks in the minor groove

Aspects of Soft and Spontaneous CP Violation

We study four different models for CP violation: the standard (KM) model, the aspon model of spontaneous breaking and two models of soft breaking. In all except the standard model, the strong CP problem is addressed and solved. Testable predictions for the area of the unitarity triangle and for (epsilon'/epsilon)_K are emphasized. The issue of CP violation may well become the first place where the standard model of particle theory is shown definitively to be deficient. There are two reasons for expecting this to happen: (1) the strong CP problem is still not understood in the unadorned standard model and (2) the KM mechanism, although unquestionably present, may not provide the full explanation of epsilon_K and (epsilon'/epsilon)_K.Comment: 24 pages LaTeX including 4 figures. Minor modification to analysis of lower bound for d_n, summarized in new Table I

Enhanced free vibration analysis of composite wing-box structures by one-dimensional Component-wise and dynamic stiffness formulations

Free vibration analysis is an important aspect of aeronautical engineering. The availability of enhanced models for accurate modal analysis is therefore of primary interest. This work deals with advanced 1D formulations able to foresee higher-order phenomena, such as elastic bending/shear coupling, restrained torsional warping and 3D strain effects. The proposed beam models are developed in the framework of the Carrera Unified Formulation (CUF), whose hierarchical capability allows the analyst to implement automatically refined models with arbitrarily rich kinematics. The capabilities of the resulting 1D theories are assessed by both weak- and strong-form solutions and the results from free vibration analyses of wing-like composite structures are compared to those from the literature, experiments and commercial FEM software

Quantum Erasure by Transverse Indistinguishability

We show that the first experiment with double-slits and twin photons detected in coincidence can be understood as a quantum eraser. The ``which path'' information is erased by transverse indistinguishability obtained by means of mode filtering in the twin conjugated beam. A delayed choice quantum eraser based on the same scheme is proposed.Comment: Submitted for publication in Optics Communication

Preliminary study on the contribution of external forces to ship behavior

Computational modeling has become a prominent tool to simulate physical processes for research and development projects. The coastal region of southern Brazil is very susceptible to oil spill accidents. Currently, oil is intensively transported in the region due to the presence of the Rio Grande Harbor, the TranspetroWaterway Terminal (Petrobras) and the Riograndense S/A Oil Refinery. Therefore, simulations under ideal navigation conditions for ships with potentially polluting loads are important because their use can reduce oil spills and toxic compound accidents in the environment. Therefore, the main objective of this work is to present a preliminary study of the contribution of external forces to a ship's behavior over a simulation period of 5 h. The methodology is based on the development of a numerical model using LaGrangian formalism and the calculus of variations, besides Maneuvering Modeling Group (MMG Model). The external forces considered were the wind acting directly on the ship, waves driven by wind, the rudder, the force acting on the hull, inertial forces, and seawater density. The results indicate that at the beginning of the simulation, the inertial forces were of primary importance for controlling the trajectory of the ship. After 5 h of simulations, the ship had completely changed its trajectory due to forces suffered by the ship, classified according to MMG Model

Explaining the Higgs Decays at the LHC with an Extended Electroweak Model

We show that the recent discovery of a new boson at the LHC, which we assume to be a Higgs boson, and the observed enhancement in its diphoton decays compared to the SM prediction, can be explained by a new doublet of charged vector bosons from an extended electroweak gauge sector model with SU(3)_C\otimesSU(3)_L\otimesU(1)_X symmetry. Our results show a good agreement between our theoretical expected sensitivity to a 126--125 GeV Higgs boson and the experimental significance observed in the diphoton channel at the 8 TeV LHC. Effects of an invisible decay channel for the Higgs boson are also taken into account, in order to anticipate a possible confirmation of deficits in the branching ratios into $ZZ^*$, $WW^*$, bottom quarks, and tau leptons.Comment: 16 pages, 5 figure

Decomposing Noise in Biochemical Signaling Systems Highlights the Role of Protein Degradation

AbstractStochasticity is an essential aspect of biochemical processes at the cellular level. We now know that living cells take advantage of stochasticity in some cases and counteract stochastic effects in others. Here we propose a method that allows us to calculate contributions of individual reactions to the total variability of a system’s output. We demonstrate that reactions differ significantly in their relative impact on the total noise and we illustrate the importance of protein degradation on the overall variability for a range of molecular processes and signaling systems. With our flexible and generally applicable noise decomposition method, we are able to shed new, to our knowledge, light on the sources and propagation of noise in biochemical reaction networks; in particular, we are able to show how regulated protein degradation can be employed to reduce the noise in biochemical systems

Serologic evidence for an epizootic dengue virus infecting toque macaques (Macaca sinica) at Polonnaruwa, Sri Lanka

Dengue is one of the most rapidly emerging diseases in the tropics. Humans are the principal reservoir of dengue viruses. It is unclear if nonhuman primates also serve as a reservoir of human dengue viruses under certain conditions. In this study, a cross-sectional serologic survey was carried out to characterize the pattern of transmission of a recently identified dengue virus among toque macaques in Sri Lanka. The results indicated that an epizootic dengue virus was active among the macaques. A single epizootic had taken place between October 1986 and February 1987 during which 94% of the macaques within the 3 km2 study site were exposed to the virus. The epizootic was highly focal in nature because macaques living 5 km from the study population were not exposed to the virus. The transmission of dengue viruses among macaques in the wild may have important public health implications

Random field simulation over curved surfaces: Applications to computational structural mechanics

It is important to account for inherent variability in the material properties in the design and analysis of engineering structures. These properties are typically not homogeneous, but vary across the spatial coordinates within a structure, as well as from specimen to specimen. This form of uncertainty is commonly modelled using random fields within the Stochastic Finite Element Method. Simulation within this framework can be complicated by the dependence of a random field’s correlation function upon the geometry of the domain over which it is defined. In this paper, a new method is proposed for simulating random fields over a general two-dimension curved surface, represented as a finite element mesh. The covariance function is parametrised using the geodesic distance, evaluated using the solution to the ‘discrete geodesic problem,’ and a point discretisation approach is subsequently applied in order to sample the random field at the nodes of the model. The major contribution of the present work is the development of a methodology for simulating random fields over curved surfaces of arbitrary geometry, with a focus upon non-intrusive application to industrial finite element models using ‘off the shelf’ commercial software. In order to demonstrate the potential impact of the proposed approach, the algorithm is applied in an uncertainty quantification case study concerning vibration and buckling of an industrial composite aircraft wing model