ATR Contributes More Than ATM in Intra-S-Phase Checkpoint Activation after IR,and DNA-PKcs Facilitates Recovery: Evidence for Modular Integration of ATM/ATR/DNA-PKcs Functions

The intra-S-phase checkpoint was among the first reported cell cycle checkpoints in mammalian cells. It transiently slows down the rate of DNA replication after DNA damage to facilitate repair and thus prevents genomic instability. The ionizing radiation (IR)-induced intra-S-phase checkpoint in mammalian cells is thought to be mainly dependent upon the kinase activity of ATM. Defects in the intra-S-phase checkpoint result in radio-resistant DNA synthesis (RDS), which promotes genomic instability. ATM belongs to the PI3K kinase family along with ATR and DNA-PKcs. ATR has been shown to be the key kinase for intra-S-phase checkpoint signaling in yeast and has also been implicated in this checkpoint in higher eukaryotes. Recently, contributions of DNA-PKcs to IR-induced G₂-checkpoint could also be established. Whether and how ATR and DNA-PKcs are involved in the IR-induced intra-S-phase checkpoint in mammalian cells is incompletely characterized. Here, we investigated the contributions of ATM, ATR, and DNA-PKcs to intra-S-phase checkpoint activation after exposure to IR of human and hamster cells. The results suggest that the activities of both ATM and ATR are essential for efficient intra-S-phase checkpoint activation. Indeed, in a wild-type genetic background, ATR inhibition generates stronger checkpoint defects than ATM inhibition. Similar to G2 checkpoint, DNA-PKcs contributes to the recovery from the intra-S-phase checkpoint. DNA-PKcs–deficient cells show persistent, mainly ATR-dependent intra-S-phase checkpoints. A correlation between the degree of DSB end resection and the strength of the intra-S-phase checkpoint is observed, which again compares well to the G2 checkpoint response. We conclude that the organization of the intra-S-phase checkpoint has a similar mechanistic organization to that of the G₂ checkpoint in cells irradiated in the G₂ phase.     

Peptides Containing meso-Oxa-Diaminopimelic Acid as Substrates for the Cell-Shape-Determining Proteases Csd6 and Pgp2

The enzymes Csd6 and Pgp2 are peptidoglycan (PG) proteases found in the pathogenic bacteria Helicobacter pylori and Campylobacter jejuni, respectively. These enzymes are involved in the trimming of non-crosslinked PG sidechains and catalyze the cleavage of the bond between meso-diaminopimelic acid (meso-Dap) and d -alanine, thus converting a PG tetrapeptide into a PG tripeptide. They are known to be cell-shape-determining enzymes, because deletion of the corresponding genes results in mutant strains that have lost the normal helical phenotype and instead possess a straight-rod morphology. In this work, we report two approaches directed towards the synthesis of the tripeptide substrate Ac-iso-d -Glu-meso-oxa-Dap-d -Ala, which serves as a mimic of the terminus of an non-crosslinked PG tetrapeptide substrate. The isosteric analogue meso-oxa-Dap was utilized in place of meso-Dap to simplify the synthetic procedure. The more efficient synthesis involved ring opening of a peptide-embedded aziridine by a serine-based nucleophile. A branched tetrapeptide was also prepared as a mimic of the terminus of a crosslinked PG tetrapeptide. We used MS analysis to demonstrate that the tripeptide serves as a substrate for both Csd6 and Pgp2 and that the branched tetrapeptide serves as a substrate for Pgp2, albeit at a significantly slower rate.     

Tracking model of an adaptive lattice filter for a linear chirp FMsignal in noise

The paper studies the behavior of the partial correlation (PARCOR) coefficients and the output misadjustment of the stochastic gradient adaptive lattice filter in response to a complex linear chirp FM signal in white Gaussian noise. Analytic expressions for the optimal PARCOR coefficients of the filter are derived. Analytic as well as iterative models for a three-stage filter are also derived. The analytic expressions show that the tracking and convergence properties of the filter are separate phenomena. Simulation results also show that the spectral contents of the PARCOR coefficients for the stochastic gradient update algorithm consist of a stationary and a linearly swept component. A single-stage model is developed to explain this behavior. Finally, output misadjustment plots for the filter show that an optimum value for the forgetting factor can be obtained to minimize the misadjustment, but the value required to achieve local minimum misadjustment varies with each stage of the filter. It is shown that in applications where the input has a high signal-to-noise ratio (SNR), the misadjustment decreases rapidly at each successive stage, thus implying that relatively short filter lengths are sufficient to provide effective tracking     

An Approximation To The Stationary Distribution Of A Multidimensional Markov Process

In this paper we present an approximate, non-iterative method for calculating the stationary distribution of a multidimensional Markov process. Although the method has more general applications, we illustrate it for a particular example of a repairable item inventory model with returns. We analyze two versions of this model. In the first version we assume that all failed items are repairable, whereas in the second version we assume that some of the failed items are irreparable and hence are scrapped. Each version gives rise to multidimensional state spaces that are extremely large even for problems with a relatively small number of items. Because of the large state spaces, the emphasis of this paper is on developing an approximation for the stationary distribution. We show that this approximation is not only easy to calculate but is also quite accurate across a broad range of problem parameters.     

Analysis of free edge effects in composite laminates

Extensive work has been done in the field of free edge effects in composite laminates. The present paper reviews the modelling as well as the experimental work on this class of boundary value problems. The modelling techniques developed by a number of investigators and the experimental validation of the predictions made through these models are discussed.     

Carboxymethylation of Cassia tora gum

The preparation of carboxymethyl (CM)–Cassia tora gum (CTG) with monochloroacetic acid and sodium hydroxide was investigated under different reaction conditions. The carboxymethylation reaction was studied with respect to the degree of substitution of CM–CTG. The variables studied were the concentration of reactants, methanol–water ratio (solvent), reaction time, and reaction temperature. Carboxymethylation of CTG increased its solubility in cold water and the stability of its paste to microorganisms. Regardless of the degree of substitution of these products, their aqueous solutions were characterized by non‐Newtonian pseudoplastic behavior. © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 89: 3216–3219, 2003     

Optical bandgap of Sb0.2Bi1.8Te3 thin films

Sb_0.2Bi_1.8Te₃ Thin Films were grown using the thermal evaporation technique on a (001) face of NaCl crystal as a substrate at room temperature. The optical absorption was measured in the wave number range 500 cm^–1 to 4000 cm^–1. From the optical absorption data the bandgap has been evaluated and studied as a function of the film thickness and deposition temperature. The data indicate absorption through direct interband transition with a bandgap around 0.21 eV. The detailed results are reported.     

Analysis of link-layer backoff schemes on point-to-point Markov fading links

Backoff algorithms are typically employed in multiple-access networks (e.g., Ethernet) to recover from packet collisions. We propose and carry out the analysis for three types of link-layer backoff schemes, namely linear backoff, exponential backoff, and geometric backoff, on point-to-point wireless fading links where packet errors occur non-independently. In such a scenario, the backoff schemes are shown to achieve better energy efficiency without compromising much on the link layer throughput performance.