Watching the DNA Repair Ensemble Dance

AbstractRepair of damaged DNA is a dynamic process that requires careful orchestration of a multitude of enzymes, adaptor proteins, and chromatin constituents. In this issue of Cell, Lisby et al. (2004) provide a visual glimpse into how the diverse signaling and repair machines are organized in space and time around the deadliest genetic lesions—the DNA double-strand breaks

Switched-Capacitor Filter Optimization with Respect to Switch On-State Resistance and Features of Real Operational Amplifiers

The optimization of a switched-capacitor filter, which implements a biquadratic section, is described in this paper. The aim of the optimization is to obtain a required magnitude frequency response of the filter. The optimization takes into account both one of the features of real switches - their on-state resistance, and the features of real operational amplifiers - finite voltage gain and finite unity-gain bandwidth. An optimal dynamic range is to be achieved as well. The differential evolution - a kind of evolutionary algorithms - is employed for the optimization. The filter is designed by the usual way with ideal switches and ideal operational amplifiers at first. The analysis of this filter with real switches and real operational amplifiers proves that there is a significant difference between its magnitude frequency response and the one with ideal components. Hence, the optimization is applied for finding component values so that the magnitude frequency response is as similar to the one with ideal components as possible. As for other main real features of operational amplifiers - input and output resistance - it is shown that their effect is small

Ways to Optimize Analogue Switched Circuits

This paper describes how analogue switched circuits (switched-capacitor and switched-current circuits) can be optimized by means of a personal computer. The optimization of this kind of circuits is not so common and their analysis is more difficult in comparison with continuously working circuits. Firstly, the nonidealities occurring in these circuits whose effect on their characteristics should be optimized are discussed. Then a few ways to analyze analogue switched circuits are shown. From all optimization algorithms applicable for this kind of optimization, two ones that seem to be the most promising are proposed. The differential evolution (one of evolutionary algorithms) combined with the simplex method was found to be most appropriate from these two ones. Two types of programs are required for the optimization of these circuits: a program for implementing calculations of the used optimization algorithm and a program for the analysis of the optimized circuit. Several suitable computer programs from both of the groups together with their proper settings according to authors’ experience are proposed. At the end of the paper, an example of a switched-current circuit optimization documenting the previous description is presented

THE ISSUE OF OBSERVANCE OF SAFE FOLLOWING DISTANCE BETWEEN VEHICLES IN GERMANY

This technical article discusses the issue of observance of safe following distance between vehicles on motorways in the Federal Republic of Germany. It contains an analysis of accident frequency on roads in Germany, with a particular focus on traffic accidents caused by the failure to observe a safe following distance behind another vehicle. Next, it describes legal requirements on the observance of a safe distance in particular countries and, in respect thereof, it presents results of an analysis of the observance of a safe following distance between vehicles on German motorways containing two and three traffic lanes per carriageway in one direction

THE ISSUE OF OBSERVANCE OF SAFE FOLLOWING DISTANCE BETWEEN VEHICLES IN GERMANY

This technical article discusses the issue of observance of safe following distance between vehicles on motorways in the Federal Republic of Germany. It contains an analysis of accident frequency on roads in Germany, with a particular focus on traffic accidents caused by the failure to observe a safe following distance behind another vehicle. Next, it describes legal requirements on the observance of a safe distance in particular countries and, in respect thereof, it presents results of an analysis of the observance of a safe following distance between vehicles on German motorways containing two and three traffic lanes per carriageway in one direction

The World of Fast Moving Objects

The notion of a Fast Moving Object (FMO), i.e. an object that moves over a distance exceeding its size within the exposure time, is introduced. FMOs may, and typically do, rotate with high angular speed. FMOs are very common in sports videos, but are not rare elsewhere. In a single frame, such objects are often barely visible and appear as semi-transparent streaks. A method for the detection and tracking of FMOs is proposed. The method consists of three distinct algorithms, which form an efficient localization pipeline that operates successfully in a broad range of conditions. We show that it is possible to recover the appearance of the object and its axis of rotation, despite its blurred appearance. The proposed method is evaluated on a new annotated dataset. The results show that existing trackers are inadequate for the problem of FMO localization and a new approach is required. Two applications of localization, temporal super-resolution and highlighting, are presented

Dynamic assembly and sustained retention of 53BP1 at the sites of DNA damage are controlled by Mdc1/NFBD1

53BP1 is a key component of the genome surveillance network activated by DNA double strand breaks (DSBs). Despite its known accumulation at the DSB sites, the spatiotemporal aspects of 53BP1 interaction with DSBs and the role of other DSB regulators in this process remain unclear. Here, we used real-time microscopy to study the DSB-induced redistribution of 53BP1 in living cells. We show that within minutes after DNA damage, 53BP1 becomes progressively, yet transiently, immobilized around the DSB-flanking chromatin. Quantitative imaging of single cells revealed that the assembly of 53BP1 at DSBs significantly lagged behind Mdc1/NFBD1, another DSB-interacting checkpoint mediator. Furthermore, short interfering RNA-mediated ablation of Mdc1/NFBD1 drastically impaired 53BP1 redistribution to DSBs and triggered premature dissociation of 53BP1 from these regions. Collectively, these in vivo measurements identify Mdc1/NFBD1 as a key upstream determinant of 53BP1's interaction with DSBs from its dynamic assembly at the DSB sites through sustained retention within the DSB-flanking chromatin up to the recovery from the checkpoint