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Biomedical subjects

Michael Lewis

Publications and source records attributed to Michael Lewis.

At least 37 records · Page 2Linked to original sources
PubMed2005

Cytosine catalysis of nitrosative guanine deamination and interstrand cross-link formation.

Effects are discussed of the anisotropic DNA environment on nitrosative guanine deamination based on results of an ab initio study of the aggregate 3 formed by guaninediazonium ion 1 and cytosine 2. Within 3, the protonation of 2 by 1 is fast and exothermic and forms 6, an aggregate between betaine 4 (2-diazonium-9H-purin-6-olate) and cytosinium ion 5. Electronic structure analysis of 4 shows that this betaine is not mesoionic; only the negative charge is delocalized in the pi-system while the positive charge resides in the sigma-system. Potential energy surface exploration shows that both dediazoniation and ring-opening of betaine 4 in aggregate 6 are fast and exothermic and lead irreversibly to E-11, the aggregate between (E)-5-cyanoimino-4-oxomethylene-4,5-dihydroimidazole E-10 and 5. The computed pair binding energies for 3, 6, and E-11 greatly exceed the GC pair binding energy. While 1 can be a highly reactive intermediate in reactions of the "free nucleobase" (or its nucleoside and nucleotide), the cyanoimine 10 emerges as the key intermediate in nitrosative guanine deamination in ds-DNA and ds-oligonucleotides. In essence, the complementary nucleobase cytosine provides base catalysis and switches the sequence of deprotonation and dediazoniation. It is argued that this environment-induced switch causes entirely different reaction paths to products as compared to the respective "free nucleobase" chemistry, and the complete consistency is demonstrated of this mechanistic model with all known experimental results. Products might form directly from 10 by addition and ring closure, or their formation might involve water catalysis via 5-cyanoamino-4-imidazolecarboxylic acid 12 and/or 5-carbodiimidyl-4-imidazolecarboxylic acid 13. The pyrimidine ring-opened intermediates 10, 12, and 13 can account for the formations of xanthosine, the pH dependency and the environment dependency of oxanosine formation, the formation of the classical cross-link dG(N(2)())-to-dG(C2), including the known sequence specificity of its formation, and the formation of the structure-isomeric cross-link dG(N1)-to-dG(C2).

Carbodiimides↗
PubMed2005

Aggression at age 5 as a function of prenatal exposure to cocaine, gender, and environmental risk.

OBJECTIVE: To examine childhood aggression at age 5 in a multiple risk model that includes cocaine exposure, environmental risk, and gender as predictors. METHODS: Aggression was assessed in 206 children by using multiple methods including teacher report, parent report, child's response to hypothetical provocations, and child's observed behavior. Also examined was a composite score that reflected high aggression across contexts. RESULTS: Multiple regression analyses indicated that a significant amount of variance in each of the aggression measures and the composite was explained by the predictors. The variables that were independently related differed depending on the outcome. Cocaine exposure, gender, and environmental risk were all related to the composite aggression score. CONCLUSIONS: Cocaine exposure, being male, and a high-risk environment were all predictive of aggressive behavior at 5 years. It is this group of exposed boys at high environmental risk that is most likely to show continued aggression over time.

Aggression↗
PubMed2005

Real-time monitoring in managing the decontamination of flexible gastrointestinal endoscopes.

OBJECTIVES: To evaluate the efficacy of endoscope reprocessing using bacteriologic methods and adenosine triphosphate (ATP) bioluminescence and to evaluate the potential benefits of the latter in managing the process. SETTING: An endoscopy unit in each of 2 acute district general hospitals in the United Kingdom. METHODS: Following visual observation, 8 locations important in the decontamination of gastrointestinal (GI) endoscopes were monitored during reprocessing by bacteriologic sampling (paddle method) and ATP bioluminescence. RESULTS: Endoscope reprocessing was conducted in accordance with British Society of Gastroenterology guidelines. Bacteriologic tests required 24 hours for results to be obtained; ATP tests were completed within 2 minutes. Of the 504 sites tested throughout the decontamination process, bacterial growth was recorded on 32 occasions, 3 from the end product. Throughout the decontamination process, ATP tests obtained 95 results above benchmark values and 1 from the end product. CONCLUSIONS: The bacteriologic results after terminal disinfection indicated that the reprocessing was carried out effectively overall. ATP results prior to disinfection indicated that manual cleaning might not have always been performed adequately and that this could have impaired the disinfection process. ATP provided a rapid means of assessing the efficacy of cleaning steps prior to terminal disinfection.

Adenosine Triphosphate↗
PubMed2005

Antecedents of emotion knowledge: Predictors of individual differences in young children.

Individual differences in emotion knowledge were examined among 188 4-year-old, predominantly African American children. Cognitive ability and negative emotionality, maternal characteristics (parenting, verbal intelligence, and depressive symptoms), environmental risk, and child sex were examined as predictors of emotion knowledge. Regression analyses indicated that cognitively skilled children who resided in relatively low risk environments with verbally intelligent mothers possessed greater emotion knowledge. Proximal (4-year) child cognitive ability was a stronger predictor than distal (2-year) cognitive ability. Positive parenting at 4 years was correlated with child emotion knowledge, but this relation disappeared when parenting was examined in the context of other predictors. These findings highlight the potential role of child cognitive ability, along with environmental risk and maternal verbal intelligence, in children's emotion knowledge and demonstrate the importance of examining a variety of predictors for their unique contribution to emotion knowledge.

Journal Article↗
PubMed2005

Young children's adjustment as a function of maltreatment, shame, and anger.

Maltreated children are at increased risk for behavior problems. This study examines a model in which shame mediates the potential relation between maltreatment and anger, and anger mediates the potential relation between shame and behavior problems. Participants were 177 children (ages 3 to 7 years) and their mothers, 90 of whom had histories of perpetrating neglect and/or physical abuse. Physical abuse, but not neglect, was related to increased shame during an evaluative task; shame was related to increased anger; and anger to teacher ratings of total behavior problems and externalizing problems. Age moderated the relation between physical abuse and adjustment, as abuse was related to more total problems only among the younger children. Anger was a significant mediator of shame and both behavior problems and externalizing problems. Shame, anger, age, and type of maltreatment appear to be important factors in explaining variance in behavioral adjustment following a history of maltreatment.

Adaptation, Psychological↗
PubMed2005

Does the Organization of Emotional Expression Change Over Time? Facial Expressivity From 4 to 12 Months.

Differentiation models contend that the organization of facial expressivity increases during infancy. Accordingly, infants are believed to exhibit increasingly specific facial expressions in response to stimuli as a function of development. This study tested this hypothesis in a sample of 151 infants (83 boys and 68 girls) observed in 4 situations (tickle, sour taste, arm restraint, and masked stranger) at 4 and 12 months of age. Three of the 4 situations showed evidence of increasing specificity over time. In response to tickle, the number of infants exhibiting joy expressions increased and the number exhibiting interest, surprise, and surprise blends decreased from 4 to 12 months. In tasting a sour substance, more infants exhibited disgust and fewer exhibited joy and interest expressions, and fear and surprise blends over time. For arm restraint, more infants exhibited anger expressions and anger blends and fewer exhibited interest and surprise expressions and surprise blends over time. In response to a masked stranger, however, no evidence of increased specificity was found. Overall, these findings suggest that infants increasingly exhibit particular expressions in response to specific stimuli during the 1st year of life. These data provide partial support for the hypothesis that facial expressivity becomes increasingly organized over time.

Journal Article↗
PubMed2005

Attentive navigation for viewpoint control in virtual environments.

Three-dimensional virtual environments and teleoperation activities depend on the ability to position an egocentric viewpoint at meaningful locations. Evidence from foundational research has led to the development of control strategies that generally adopt an all-or-nothing approach to guiding the viewer to useful vistas. This work examines attentive navigation, a technique for partially automating viewpoint control to promote a supportive yet unscripted exploration of a virtual environment. A collection of three experiments was designed to assess the effectiveness of attentive navigation versus commonly used free navigation techniques. Results show that this approach has promising consequences for improving object recognition, developing an understanding of the configuration of objects, and searching for target objects. Actual or potential applications of this research include improved interaction techniques for extracting information from visual representations, virtual environments, and teleoperation experiences.

Adolescent↗
PubMed2004

A quantitative measure of myelination development in infants, using MR images.

The objective of this study was to measure myelination of frontal lobe changes in infants and young children. Twenty-four cases of infants and children (age range 12-121 months) were evaluated by a quantitative assessment of T2-weighted MR image features. Reliable quantitative changes between white and gray matter correlated with developmental age in a group of children with no neurological findings. Myelination appears to be an increasing exponential function with the greatest rate of change occurring over the first 3 years of life. The quantitative changes observed were in accordance with previous qualitative judgments of myelination development. Children with periventricular leukomalacia (PVL) showed delays in achieving levels of myelination when compared to normal children and adjusted for chronological age. The quantitative measure of myelination development may prove to be useful in assessing the stages of development and helpful in the quantitative descriptions of white matter disorders such as PVL.

Aging↗
PubMed2004

Physiological and Emotional Reactivity to Learning and Frustration.

This study examined the behavioral (arm, facial) autonomic (heart rate, respiratory sinus arrhythmia [RSA], and adrenocortical axis) reactivity of 56 4-month-old infants in response to contingency learning and extinction-induced frustration. During learning, infants displayed increases in operant arm response and positive emotional expressions. Changes in average RSA(V(NA)) paralleled the observed changes in facial expressions in general and maintained an inverse relation with heart rate throughout most of the session. When frustrated by extinction, infants displayed increases in negative expressions, heart rate, and a brief increase in RSA(V(NA)) followed by a significant decrease. No significant changes were observed for cortisol. These behavioral and facial responses are consistent with earlier work. The physiological changes, along with the facial expressions and instrumental responses, indicate that the autonomic nervous system functions as a coordinated affect system by 4 months of age.

Journal Article↗
PubMed2004

On Specifying Specificity: Facial Expressions at 4 Months.

Izard (2004/this issue) clarifies the position of differential emotions theory by proposing a distinction between hard and soft versions of event-emotion expression relations. We concur that the best design to examine situational specificity in facial expressions is one that utilizes multiple stimulus situations assessed over multiple occasions and ages. However, the problem of how to identify, a priori, a family of stimulus situations remains. We offer an example from our own recent work demonstrating how facial expressions and physiological indexes may converge to indicate the presence of a meaningful family of stimulus situations. Specifically, we found evidence for a family of frustrating, goal-blocking events that elicited expressions and cortisol responses indicative of anger at 4 months. Yet, individual differences exist in that these situations also elicited expressions and cortisol changes indicative of sadness. Identification of a more comprehensive set of such situations throughout infancy will allow researchers to more systematically examine the degree to which situational specificity of emotions is present.

Journal Article↗
PubMed2003

Contextual determinants of anger and other negative expressions in young infants.

Two experiments examined how different frustration contexts affect the instrumental and emotional responses of 4- to 5-month-old infants. Three different frustrating contexts were investigated: loss of stimulation (extinction), reduction in contingent stimulation (partial reinforcement), and loss of stimulus control (noncontingency). In both experiments, changes in arm activity and facial expressions of anger and sadness coded according to the Maximally Discriminative Facial Movement Coding System (MAX) were the measures of frustration. Both experiments showed that (a) arm responses increased when the contingent stimulus was lost or reduced but decreased when control of the stimulus was lost under noncontingency, (b) MAX-coded anger, but not MAX-coded sad or blends of anger and sad, was associated with frustration, and (c) the pattern of anger and arm responses varied with the frustration context. When contingent stimulation was lost or reduced, both anger and arm responses increased, but when expected control was lost under noncontingency, arm responses decreased while anger increased.

Anger↗
PubMed2003

Inhibitory motor control at five years as a function of prenatal cocaine exposure.

This study examined children's (n = 140, age 5 years) ability to inhibit a motor response as a function of prenatal cocaine exposure. We hypothesized that cocaine-exposed children would perform worse than unexposed children on the Contrary Tapping task. Results indicated that cocaine exposure, high environmental risk, male gender, and low child IQ each were related to poorer inhibitory control. An interaction indicated that cocaine effects were specific to children who lived in relatively low-risk environments. Cocaine-exposed children made an error sooner than unexposed children in low-risk environments but in the same trial as both exposed and unexposed children living in high-risk environments. Potential underlying mechanisms and the importance of examining cocaine exposure effects in the context of children's existing environment are discussed.

Child Development↗
PubMed2003

The emergence of consciousness and its role in human development.

In this paper, I talk about several issues in regard to self and consciousness. I do so from a developmental perspective, since such a perspective may provide a framework to help understand consciousness as seen in the adult human. Briefly, the two processes I will call the machinery of the self and the mental state of the idea of me develop over the first two years of the child's life. Moreover, and perhaps of equal importance is the fact that the development of consciousness (the idea of me) provides the scaffolding for the development of the child's social and emotional development and is the first step in the child's development of other mental states, which provide the underpinning of a theory of mind. I will first explore what a self is and what it is not; then I will present a developmental model that provides a way of measuring early the idea of me or consciousness. Having shown how to measure this mental state, I will show how it has an impact on the development of a theory of mind, as well as on the child's emotional and social life. Finally, I will turn to the emergence of explicit and implicit consciousness.

Consciousness↗
PubMed2003

The impact of organizational change on social work staffing in a hospital setting: a national, longitudinal study of social work in hospitals.

Market forces continue to shape the health care environment, producing radical changes within the hospital. These changes are affecting social work structure, staffing, and processes within the hospital setting, particularly in the area of social work staffing. This paper examines the changes impacting hospital settings over three fiscal years. A primary question is whether or not social work staffing is being negatively impacted by these hospital changes, and what factors predict the downsizing of social work staff.

Health Services Research↗
PubMed2002

The genotype distribution of the XRCC1 gene indicates a role for base excision repair in the development of therapy-related acute myeloblastic leukemia.

Polymorphisms in several DNA repair genes have been described. These polymorphisms may affect DNA repair capacity and modulate cancer susceptibility by means of gene-environment interactions. We investigated DNA repair capacity and its association with acute myeloblastic leukemia (AML). We studied polymorphisms in 3 DNA repair genes: XRCC1, XRCC3, and XPD. We also assessed the incidence of a functional polymorphism in the NQO1 gene, which is involved in protection of cells from oxidative damage. We genotyped the polymorphisms by using polymerase chain reaction-restriction fragment-length polymorphism analysis in 134 patients with de novo AML, 34 with therapy-related AML (t-AML), and 178 controls. The distributions of the XRCC3 Thr241Met and NQO1 Pro187Ser genotypes were not significantly different in patients and controls. However, the distribution of the XRCC1 Arg399Gln genotypes was significantly different when comparing the t-AML and control groups (chi(2), P =.03). The presence of at least one XRCC1 399Gln allele indicated a protective effect for the allele in controls compared with patients with t-AML (odds ratio 0.44; 95% confidence interval, 0.20-0.93). We found no interactions between the XRCC1 or XRCC3 and NQO1 genotypes. We also found no differences in the distribution of the XPD Lys751Gln or XRCC1 Arg194Trp genotypes. Our data provide evidence of a protective effect against AML in individuals with at least one copy of the variant XRCC1 399Gln allele compared with those homozygous for the common allele.

Adolescent↗
PubMed2002

Synergism of catalysis and reaction center rehybridization in nucleophilic additions to cumulenes: the one-, two-, three-water hydrolyses of carbodiimide and methyleneimine.

The results of a theoretical study of the one-, two- and three-water hydrolyses of carbodiimide and the one- and two-water hydrolyses of methyleneimine are presented. All structures were optimized and characterized at the MP2(full)/6-31G* level of theory. Energies for the one-water hydrolysis of carbodiimide were determined at numerous higher levels of theory, up to the QCISD(T)(fc)/6-311+G(3df,2p)//MP2(full)/6-31G* level. The Delta E0(Delta G298) activation barriers for the rate-determining steps of the one-, two- and three-water hydrolyses of carbodiimide, respectively, are 44.8 (46.3), 29.3 (32.3) and 22.9 (26.2) kcal mol(-1) at the MP2(full)/6-31G* level. The consideration of a second water molecule catalyzes the hydrolysis by 15.5 kcal mol(-1) on the E0 surface and by 14.0 kcal mol(-1) on the G298 surface with respect to the one-water hydrolysis. Placement of a third water molecule opposite the site of proton transfer catalyzes the reaction by an additional 6.4 kcal mol(-1) on the E0 surface and by 6.1 kcal mol(-1) on the G298 surface. The catalytic effect of the third water molecule results from the synergistic effects of rehybridization and charge relaxation in the transition state. The charge relaxation in the transition state is illustrated through natural population analysis calculations on the pre-coordination complexes and the transition state structures. We also consider the placement of the third water molecule in the proton transfer chain and we show this to be of little catalytic relevance. The activation barriers determined for the one- and two-water hydrolyses of methyleneimine are Delta G298=51.9 and Delta G298=35.5 kcal mol(-1), respectively, and they are larger than for carbodiimide. The results are compared with the hydrolyses of carbon dioxide and formaldehyde.

Carbodiimides↗
PubMed2002

The azine bridge as a conjugation stopper: an NMR spectroscopic study of electron delocalization in acetophenone azines.

Dipole parallel-alignment of organic molecular crystals of azines has been achieved with a design that was based on the hypothesis that the azine bridge is a conjugation stopper. This hypothesis has now been tested in detail, and (1)H and (13)C NMR spectroscopic data of symmetric and asymmetric acetophenone azines are presented in support of this design concept. Previous structural, ab initio, and electrochemical studies have shown that the azine bridge largely inhibits through-conjugation in molecules with the general structure DPhC(Me) [double bond] N [bond] N [double bond] C(Me)PhA, where D is a donor group and A is an acceptor group. NMR spectroscopy is an excellent tool to probe the degree of conjugation through the azine bridge. The NMR results reported here for nine symmetrical and 18 asymmetrical azines show in a compelling fashion that the hypothesis holds. Varying the donor group does not change the chemical shifts of the aromatic hydrogen and carbon atoms on the acceptor-substituted phenyl ring. Likewise, varying the acceptor group does not change the chemical shifts of the atoms in the donor-substituted phenyl ring.

Acetophenones↗