N‐terminus of hMLH1 confers interaction of hMutLα and hMutLβ with hMutSα

Mismatch repair is a highly conserved system that ensures replication fidelity by repairing mispairs after DNA synthesis. In humans, the two protein heterodimers hMutSα (hMSH2‐hMSH6) and hMutLα (hMLH1‐hPMS2) constitute the centre of the repair reaction. After recognising a DNA replication error, hMutSα recruits hMutLα, which then is thought to transduce the repair signal to the excision machinery. We have expressed an ATPase mutant of hMutLα as well as its individual subunits hMLH1 and hPMS2 and fragments of hMLH1, followed by examination of their interaction properties with hMutSα using a novel interaction assay. We show that, although the interaction requires ATP, hMutLα does not need to hydrolyse this nucleotide to join hMutSα on DNA, suggesting that ATP hydrolysis by hMutLα happens downstream of complex formation. The analysis of the individual subunits of hMutLα demonstrated that the hMutSα–hMutLα interaction is predominantly conferred by hMLH1. Further experiments revealed that only the N‐terminus of hMLH1 confers this interaction. In contrast, only the C‐terminus stabilised and co‐immunoprecipitated hPMS2 when both proteins were co‐expressed in 293T cells, indicating that dimerisation and stabilisation are mediated by the C‐terminal part of hMLH1. We also examined another human homologue of bacterial MutL, hMutLβ (hMLH1–hPMS1). We show that hMutLβ interacts as efficiently with hMutSα as hMutLα, and that it predominantly binds to hMutSα via hMLH1 as well

HPF to OpenMP on the Origin2000: a case study

The geophysics group at CRS4 has long developed echo reconstruction codes in HPF on distributed-memory machines. Now, however, with the arrival of shared-memory machines and their native OpenMP compilers, the transfer to OpenMP would seem to present the logical next step in our code development strategy. Recent experience with porting one of our important HPF codes to OpenMP does not bear this out—at least not on the Origin2000. The OpenMP code suffers from the immaturity of the standard, and the operating system's handling of UNIX threads seems to severely penalize OpenMP performance. On the other hand, the HPF code on the Origin2000 is fast, scalable and not disproportionately sensitive to load on the machine.1147–1154Pubblicat

Development of a ROT22 - DATAMAP interface

This report (Contract NAS2-10331- Mod 10), outlines the development and validation of an interface between the three-dimensional transonic analysis program ROT22 and the Data from Aeromechanics Test and Analytics-Management and Analysis Package (DATAMAP). After development of the interface, the validation is carried out as follows. First, the DATAMAP program is used to analyze a portion of the Tip Aerodynamics and Acoustics Test (TAAT) data. Specifically, records 2872 and 2873 are analyzed at an azimuth of 90 deg, and record 2806 is analyzed at 60 deg. Trim conditions for these flight conditions are then calculated using the Bell performance prediction program ARAM45. Equivalent shaft, pitch, and twist angles are calculated from ARAM45 results and used as input to the ROT22 program. The interface uses the ROT22 results and creates DATAMAP information files from which the surface pressure contours and sectional pressure coefficients are plotted. Twist angles input to ROT22 program are then iteratively modified in the tip region until the computed pressure coefficients closely match the measurements. In all cases studied, the location of the shock is well predicted. However, the negative pressure coefficients were underpredicted. This could be accounted for by blade vortex interaction effects

Transition Properties of Low Lying States in Atomic Indium

We present here the results of our relativistic many-body calculations of various properties of the first six low-lying excited states of indium. The calculations were performed using the relativistic coupled-cluster method in the framework of the singles, doubles and partial triples approximation. We obtain a large lifetime ~10s for the [4p^6]5s^2 5p_{3/2} state, which had not been known earlier. Our precise results could be used to shed light on the reliability of the lifetime measurements of the excited states of atomic indium that we have considered in the present work.Comment: 6 pages, 1 figure and 3 table

Cellular automaton model of precipitation/dissolution coupled with solute transport

Precipitation/dissolution reactions coupled with solute transport are modelled as a cellular automaton in which solute molecules perform a random walk on a regular lattice and react according to a local probabilistic rule. Stationary solid particles dissolve with a certain probability and, provided solid is already present or the solution is saturated, solute particles have a probability to precipitate. In our simulation of the dissolution of a solid block inside uniformly flowing water we obtain solid precipitation downstream from the original solid edge, in contrast to the standard reaction-transport equations. The observed effect is the result of fluctuations in solute density and diminishes when we average over a larger ensemble. The additional precipitation of solid is accompanied by a substantial reduction in the relatively small solute concentration. The model is appropriate for the study of the r\^ole of intrinsic fluctuations in the presence of reaction thresholds and can be employed to investigate porosity changes associated with the carbonation of cement.Comment: LaTeX file, 13 pages. To appear in Journal of Statistical Physics (Proceedings of Lattice Gas'94, June 1994, Princeton). Figures available from author. Requests may be submitted by E-mail ([email protected]) or ordinary mail (Paul Scherrer Institute, CH-5232 Villigen PSI, Switzerland

Phase Shift Plus Interpolation: a scheme for high performance echo-reconstructive imaging

Echo-reconstruction techniques for non-intrusive imaging have wide application, from subsurface and underwater imaging to medical and industrial diagnostics. The techniques are based on experiments in which a collection of short acoustic or electromagnetic impulses, emitted at the surface, illuminate a certain volume and are backscattered by inhomogeneities of the medium. The inhomogeneities act as reecting surfaces or interfaces which cause signal echoing; the echoes are then recorded at the surface and processed through a "computational lens" defined by a propagation model to yield an image of the same inhomogeneities. The most sophisticated of these processing techniques involve simple acoustic imaging in seismic exploration, for which the huge data sets and stringent performance requirements make high performance computing essential. Migration, based on the scalar wave equation, is the standard imaging technique for seismic applications [1]. In the migration process, the recorded pressure waves are used as initial conditions for a wave field governed by the scalar wave equation in an inhomogeneous medium. Any migration technique begins with an a priori estimate of the velocity field obtained from well logs and an empirical analysis of seismic traces. By interpreting migrated data, comparing the imaged interfaces with the discontinuities of the estimated velocity model, insuficiencies of the velocity field can be detected and the estimate improved [2], allowing the next migration step to image more accurately. The iterative process (turnaround) of correcting to a velocity model consistent with the migrated data can last several computing weeks, and is particularly crucial for imaging complex geological structures, including those which are interesting for hydrocarbon prospecting. Subsurface depth imaging, being as it is the outcome of repeated steps of 3D seismic data migration, requires Gbytes of data which must be reduced, transformed, visualized and interpreted to obtain meaningful information. Severe performance requirements have led in the direction of high performance computing hardware and techniques. In addition, an enormous effort has historically gone into simplifying the migration model so as to reduce the cost of the operation while retaining the essential features of the wave propagation. The phase-shift-plus-interpolation (PSPI) algorithm can be an effective method for seismic migration using the "one-way" scalar wave equation; it is particularly well suited to data parallelism because of, among other things, its decoupling of the problem in the frequency domain.126-132Pubblicat

3D spectral reverse time migration with no-wraparound absorbing conditions

Comparative studies of methods of reverse time migration (RTM) show that spectral methods for calculating the Laplacian impose the least stringent demands on discretization stepsize; thus with spectral methods, the grid refinements often required by other methods can be avoided. Implemented with absorbing boundary conditions, which are energy-tuned to give good absorption at the boundaries, these spectral methods can be used effectively for migration, without suffering the problems of wraparound which have traditionally plagued them (Furumyra and Takenaka, 1995).1925-192

Montecarlo wavefield imaging of 3D prestack data

We present a new imaging methodology based on the depth extrapolation of a single dataset obtained by randomly compressing sources and shot-gathers. In this work a Monte Carlo imaging condition was implemented with a Phase Shift Plus Interpolation (PSPI) extrapolating kernel and tested on the SEG-EAGE salt model. This study demonstrates that wavefield 3D prestack depth migration is possible for industrial applications, providing high quality results in reasonable computational times

Too much of a good thing? On the relationship between CSR and employee work addiction

Recent research highlights the positive effects of organizational CSR engagement on employee outcomes, such as job and life satisfaction, performance, and trust. We argue that the current debate fails to recognize the potential risks associated with CSR. In this study, we focus on the risk of work addiction. We hypothesize that CSR has per se a positive effect on employees and can be classified as a resource. However, we also suggest the existence of an array of unintended negative effects of CSR. Since CSR positively influences an employee’s organizational identification, as well as his or her perception of engaging in meaningful work, which in turn motivates them to work harder while neglecting other spheres of their lives such as private relationships or health, CSR indirectly increases work addiction. Accordingly, organizational identification and work meaningfulness both act as buffering variables in the relationship, thus suppressing the negative effect of CSR on work addiction, which weakens the positive role of CSR in the workplace. Drawing on a sample of 565 Swiss employees taken from the 2017 Swiss Public Value Atlas dataset, our results provide support for our rationale. Our results also provide evidence that the positive indirect effects of organizational CSR engagement on work addiction, via organizational identification and work meaningfulness, become even stronger when employees care for the welfare of the wider public (i.e., the community, nation, or world). Implications for research and practice are discussed