Repair of abasic sites in DNA

Repair of both normal and reduced AP sites is activated by AP endonuclease, which recognizes and cleaves a phosphodiester bond 5' to the AP site. For a short period of time an incised AP site is occupied by poly(ADP-ribose) polymerase and then DNA polymerase beta adds one nucleotide into the repair gap and simultaneously removes the 5'-sugar phosphate. Finally, the DNA ligase III/XRCC1 complex accomplishes repair by sealing disrupted DNA ends. However, long-patch BER pathway, which is involved in the removal of reduced abasic sites, requires further DNA synthesis resulting in strand displacement and the generation of a damage-containing flap that is later removed by the flap endonuclease. Strand-displacement DNA synthesis is accomplished by DNA polymerase delta/epsilon and DNA ligase I restores DNA integrity. DNA synthesis by DNA polymerase delta/epsilon is dependent on proliferating cell nuclear antigen, which also stimulates the DNA ligase I and flap endonuclease. These repair events are supported by multiple protein-protein interactions. (C) 2003 Elsevier B.V. All rights reserved.

A novel repair model for imperfect maintenance

Commonly used repair rate models for repairable systems in the reliability literature are renewal processes, generalised renewal processes or non-homogeneous Poisson processes. In addition to these models, geometric processes (GP) are studied occasionally. The GP, however, can only model systems with monotonously changing (increasing, decreasing or constant) failure intensities. This paper deals with the reliability modelling of failure processes for repairable systems where the failure intensity shows a bathtub-type non-monotonic behaviour. A new stochastic process, i.e. an extended Poisson process, is introduced in this paper. Reliability indices are presented, and the parameters of the new process are estimated. Experimental results on a data set demonstrate the validity of the new process.

A novel repair model for imperfect maintenance

The basic repair rate models for repairable systems may be homogeneous Poisson processes, renewal processes or nonhomogeneous Poisson processes. In addition to these models, geometric processes are studied occasionally. Geometric processes, however, can only model systems with monotonously changing (increasing, decreasing or constant) failure intensity. This paper deals with the reliability modelling of the failure process of repairable systems when the failure intensity shows a bathtub type non-monotonic behaviour. A new stochastic process, an extended Poisson process, is introduced. Reliability indices and parameter estimation are presented. A comparison of this model with other repair models based on a dataset is made.

The effect of cleft lip and palate, and the timing of lip repair on mother-infant interactions and infant development

Background: Children with cleft lip and palate are at risk for psychological problems. Difficulties in mother-child interactions may be relevant, and could be affected by the timing of lip repair. Method: We assessed cognitive development, behaviour problems, and attachment in 94 infants with cleft lip (with and without cleft palate) and 96 non-affected control infants at 18 months; mother-infant interactions were assessed at two, six and 12 months. Index infants received either 'early', neonatal, lip repair, or 'late' repair (3-4 months). Results: Index infants did not differ from controls on measures of behaviour problems or attachment, regardless of timing of lip repair; however, infants having late lip repair performed worse on the Bayley Scales of Mental Development; the cognitive development of early repair infants was not impaired. Difficulties in early mother-infant interactions mediated the effects of late lip repair on infant cognitive outcome. Conclusions: Early interaction difficulties between mothers and infants having late repair of cleft lip are associated with poor cognitive functioning at 18 months. Interventions to facilitate mother-infant interactions prior to surgical lip repair should be explored.

Does repairing a cleft lip neonatally have any effect on the longer-term attractiveness of the repair?

Objective: To determine whether attractiveness and success of surgical outcome differ according to the timing of cleft lip repair. Design: Three experiments were conducted: (1) surgeons rated postoperative medical photographs of infants having either neonatal or 3-month lip repair; (2) lay panelists rated the same photographs; (3) lay panelists rated dynamic video displays of the infants made at 12 months. Normal comparison infants were also rated. The order of stimuli was randomized, and panelists were blind to timing of lip repair and the purposes of the study. Setting: Four U.K. regional centers for cleft lip and palate. Participants: Infants with isolated clefts of the lip, with and without palate. Intervention: Early lip repair was conducted at median age 4 days (inter-quartile range [IQR] = 4), and late repair at 104 days (IQR = 57). Main Outcome Measures: Ratings of surgical outcome (Experiment 1 only) and attractiveness (all experiments) on 5-point Likert scales. Results: In Experiment 1 success of surgical outcome was comparable for early and late repair groups (difference = -0.08; 95% confidence interval [CI] = -0.43 to 0.28; p = .66). In all three experiments, attractiveness ratings were comparable for the two groups. Differences were, respectively, 0.10 (95% CI = -2.3 to 0.44, p = .54); -0.11 (95% CI = -0.42 to -0.19, p = .54); and 0.08 (95% CI = -0.11 to 0.28, p =.41). Normal infants were rated more attractive than index infants (difference = 0.38; 95% CI = 0.24 to 0.52; p < .001). Conclusion: Neonatal repair for cleft of the lip confers no advantage over repair at 3 months in terms of perceived infant attractiveness or success of surgical outcome.

Impedance mismatch: some differences between the way humans and robots control interaction forces

In over forty years of research robots have made very little progress still largely confined to industrial manufacture and cute toys, yet in the same period computing has followed Moores Law where the capacity double roughly every two years. So why is there no Moores Law for robots? Two areas stand out as worthy of research to speedup progress. The first is to get a greater understanding of how human and animal brains control movement, the second to build a new generation of robots that have greater haptic sense, that is a better ability to adapt to the environment as it is encountered. A remarkable property of the cognitive-motor system in humans and animals is that it is slow. Recognising an object may take 250 mS, a reaction time of 150 mS is considered fast. Yet despite this slow system we are well designed to allow contact with the world in a variety of ways. We can anticipate an encounter, use the change of force as a means of communication and ignore sensory cues when they are not relevant. A better understanding of these process has allowed us to build haptic interfaces to mimic the interaction. Emerging from this understanding are new ways to control the contact between robots, the user and the environment. Rehabilitation robotics has all the elements in the subject to not only enable and change the lives of people with disabilities, but also to facilitate revolution change in classic robotics.

Mismatch effects on discrete-time poles

The presence of mismatch between controller and system is considered. A novel discrete-time approach is used to investigate the migration of closed-loop poles when this mismatch occurs. Two forms of state estimator are employed giving rise to several interesting features regarding stability and performance.

Improving aircraft maintenance, repair, and overhaul: A novel text mining approach

Aircraft Maintenance, Repair and Overhaul (MRO) feedback commonly includes an engineer’s complex text-based inspection report. Capturing and normalizing the content of these textual descriptions is vital to cost and quality benchmarking, and provides information to facilitate continuous improvement of MRO process and analytics. As data analysis and mining tools requires highly normalized data, raw textual data is inadequate. This paper offers a textual-mining solution to efficiently analyse bulk textual feedback data. Despite replacement of the same parts and/or sub-parts, the actual service cost for the same repair is often distinctly different from similar previously jobs. Regular expression algorithms were incorporated with an aircraft MRO glossary dictionary in order to help provide additional information concerning the reason for cost variation. Professional terms and conventions were included within the dictionary to avoid ambiguity and improve the outcome of the result. Testing results show that most descriptive inspection reports can be appropriately interpreted, allowing extraction of highly normalized data. This additional normalized data strongly supports data analysis and data mining, whilst also increasing the accuracy of future quotation costing. This solution has been effectively used by a large aircraft MRO agency with positive results.

Mechanism of the Escherichia coli DNA T:G-mismatch endonuclease (Vsr protein) probed with thiophosphate-containing oligodeoxynucleotides

The mechanism of the Escherichia coli DNA T:G mismatch endonuclease (Vsr) has been investigated using oligodeoxynucleotides substituted, at the scissile phosphate, with isomeric phosphorothioates and a 3'-phosphorothiolate. Binding and kinetic data with the phosphorothioates/phosphorothiolate indicate that the two magnesium ions, which constitute essential co-factors, are required to stabilise the extra negative charge developed on the phosphate as the transition state is formed. Additionally one of the magnesium ions serves to activate the leaving group (the non-bridging 3'-oxygen atom of the scissile phosphate) during the hydrolysis reaction. Stereochemical analysis, using the R-p phosphorothioate isomer, indicates that Vsr carries out a hydrolytic reaction with inversion of stereochemistry at phosphorus, compatible with an in-line attack of water and a pentacovalent transition state with trigonal bipyramidal geometry. In conjunction with structures of Vsr bound to its products, these data allow the reconstruction of the enzyme-substrate complex and a comprehensive description of the hydrolysis mechanism. (c) 2005 Elsevier Ltd. All rights reserved.

Asymmetric response of demand-supply mismatch to investor's sentiment

We look through both the demand and supply side information to understand dynamics of price determination in the real estate market and examine how accurately investors’ attitudes predict the market returns and thereby flagging off extent of any demand-supply mismatch. Our hypothesis is based on the possibility that investors’ call for action in terms of their buy/sell decision and adjustment in reservation/offer prices may indicate impending demand-supply imbalances in the market. In the process, we study several real estate sectors to inform our analysis. The timeframe of our analysis (1995-2010) allows us to observe market dynamics over several economic cycles and in various stages of those cycles. Additionally, we also seek to understand how investors’ attitude or the sentiment affects the market activity over the cycles through asymmetric responses. We test our hypothesis variously using a number of measures of market activity and attitude indicators within several model specifications. The empirical models are estimated using Vector Error Correction framework. Our analysis suggests that investors’ attitude exert strong and statistically significant feedback effects in price determination. Moreover, these effects do reveal heterogeneous responses across the real estate sectors. Interestingly, our results indicate the asymmetric responses during boom, normal and recessionary periods. These results are consistent with the theoretical underpinnings.

The mechanical properties of amniotic membrane influence its effect as a biomaterial for ocular surface repair

The human amniotic membrane (AM) is a tissue of fetal origin and has proven to be clinically useful as a biomaterial in the management of various ocular surface disorders including corneal stem cell transplantation. However, its success rate displays a degree of clinical unpredictability. We suggest that the measured variability inAMstiffness offers an explanation for the poor clinical reproducibility when it is used as a substrate for stem cell expansion and transplantation. Corneal epithelial stem cells were expanded upon AM samples possessing different mechanical stiffness. To investigate further the importance of biological substrate stiffness on cell phenotype we replaced AM with type I collagen gels of known stiffness. Substrate stiffness was measured using shear rheometry and surface topography was characterized using scanning electron microscopy and atomic force microscopy. The differentiation status of epithelial cells was examined using RT-PCR, immunohistochemistry and Western blotting. The level of corneal stem cell differentiation was increased in cells expanded upon AM with a high dynamic elastic shear modulus and cell expansion on type I collagen gels confirmed that the level of corneal epithelial stem cell differentiation was related to the substrate’s mechanical properties. In this paper we provide evidence to show that the preparatory method of AM for clinical use can affect its mechanical properties and that these measured differences can influence the level of differentiation within expanded corneal epithelial stem cells.

The role of double-stranded break repair in the creation of phenotypic diversity at cereal VRN1 loci

Nonhomologous repair of double-stranded breaks, although fundamental to the maintenance of genomic integrity in all eukaryotes, has received little attention as to its evolutionary consequences in the generation and selection of phenotypic diversity. Here we document the role of illegitimate recombination in the creation of novel alleles in VRN1 orthologs selected to confer adaptation to annual cropping systems in barley and wheat.

Contributions of maternal and infant factors to infant responding to the Still Face paradigm: a longitudinal study

Early mother–infant interactions are characterised by periods of synchronous interaction that are interrupted by periods of mismatch; the experience of such mismatches and their subsequent repair is held to facilitate the development of infant self-regulatory capacities (Tronick, Als, Adamson, Wise, & Brazelton, 1978). Infant responding to such interactive challenge is assumed to be a function of both maternal behaviour and pre-existing infant characteristics. However, the latter has received relatively little attention. In a prospective longitudinal study of a sample comprising high and low adversity dyads (n = 122), we examined the contributions of both maternal sensitivity and neonatal irritability to infant behavioural and physiological responding to the interactive challenge of the Still Face paradigm. Results indicated that higher levels of maternal sensitivity were associated with more regulated infant behaviour during the Still Face paradigm. Neonatal irritability also predicted poorer behavioural and heart rate recovery following the Still Face challenge. Furthermore, there was an interaction such that irritable infants with insensitive mothers showed the worst behavioural outcomes. The findings highlight the importance of the interplay between maternal and infant characteristics in determining dyadic responding.

The impact of number mismatch and passives on the real-time processing of relative clauses

Language processing plays a crucial role in language development, providing the ability to assign structural representations to input strings (e.g., Fodor, 1998). In this paper we aim at contributing to the study of children's processing routines, examining the operations underlying the auditory processing of relative clauses in children compared to adults. English-speaking children (6–8;11) and adults participated in the study, which employed a self-paced listening task with a final comprehension question. The aim was to determine (i) the role of number agreement in object relative clauses in which the subject and object NPs differ in terms of number properties, and (ii) the role of verb morphology (active vs. passive) in subject relative clauses. Even though children's off-line accuracy was not always comparable to that of adults, analyses of reaction times results support the view that children have the same structural processing reflexes observed in adults.