199 research outputs found

    Rotational master equation for cold laser-driven molecules

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    The equations of motion for the molecular rotation are derived for vibrationally cold dimers that are polarized by off-resonant laser light. It is shown that, by eliminating electronic and vibrational degrees of freedom, a quantum master equation for the reduced rotational density operator can be obtained. The coherent rotational dynamics is caused by stimulated Raman transitions, whereas spontaneous Raman transitions lead to decoherence in the motion of the quantized angular momentum. As an example the molecular dynamics for the optical Kerr effect is chosen, revealing decoherence and heating of the molecular rotation.Comment: 11 pages, 5 figures, to appear in Phys. Rev.

    Narratives for drug design

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    We explore the role of narratives of complex systems in anti-cancer drug design. We set out the value of narratives relating to cancer in promoting awareness of risky behaviour and in supporting decision-making regarding treatment options. We present cancer as a dysregulated, complex system that has emergent behaviours at multiple scales, and is governed by dynamical spatio-temporal processes. We show that this system changes structure and function in response to anti-cancer drugs, and explain that these changes are sufficiently complex to impede effective drug design. We pose what narrative might offer to support the process of drug design, providing an example of work done to date that might serve as a foundation for narrating complexity. We suggest ways of using this work combined with that of others to begin to consider narrating drug design

    Heritable patterns of tooth decay in the permanent dentition: principal components and factor analyses

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    <p>Abstract</p> <p>Background</p> <p>Dental caries is the result of a complex interplay among environmental, behavioral, and genetic factors, with distinct patterns of decay likely due to specific etiologies. Therefore, global measures of decay, such as the DMFS index, may not be optimal for identifying risk factors that manifest as specific decay patterns, especially if the risk factors such as genetic susceptibility loci have small individual effects. We used two methods to extract patterns of decay from surface-level caries data in order to generate novel phenotypes with which to explore the genetic regulation of caries.</p> <p>Methods</p> <p>The 128 tooth surfaces of the permanent dentition were scored as carious or not by intra-oral examination for 1,068 participants aged 18 to 75 years from 664 biological families. Principal components analysis (PCA) and factor analysis (FA), two methods of identifying underlying patterns without <it>a priori </it>surface classifications, were applied to our data.</p> <p>Results</p> <p>The three strongest caries patterns identified by PCA recaptured variation represented by DMFS index (correlation, r = 0.97), pit and fissure surface caries (r = 0.95), and smooth surface caries (r = 0.89). However, together, these three patterns explained only 37% of the variability in the data, indicating that <it>a priori </it>caries measures are insufficient for fully quantifying caries variation. In comparison, the first pattern identified by FA was strongly correlated with pit and fissure surface caries (r = 0.81), but other identified patterns, including a second pattern representing caries of the maxillary incisors, were not representative of any previously defined caries indices. Some patterns identified by PCA and FA were heritable (h<sup>2 </sup>= 30-65%, p = 0.043-0.006), whereas other patterns were not, indicating both genetic and non-genetic etiologies of individual decay patterns.</p> <p>Conclusions</p> <p>This study demonstrates the use of decay patterns as novel phenotypes to assist in understanding the multifactorial nature of dental caries.</p

    Natural Disaster and Risk of Psychiatric Disorders in Puerto Rican Children

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    We examined the persistence of psychiatric disorders at approximately 18 and 30 months after a hurricane among a random sample of the child and adolescent population (4–17 years) of Puerto Rico. Data were obtained from caretaker-child dyads (N = 1,886) through in person interviews with primary caretakers (all children) and youth (11–17 years) using the Diagnostic Interview Schedule for Children IV in Spanish. Logistic regressions, controlling for sociodemographic variables, were used to study the relation between disaster exposure and internalizing, externalizing, or any disorder. Children’s disaster-related distress manifested as internalizing disorders, rather than as externalizing disorders at 18 months post-disaster. At 30 months, there was no longer a significant difference in rates of disorder between hurricane-exposed and non-exposed youth. Results were similar across age ranges. Rates of specific internalizing disorders between exposed and unexposed children are provided. Research and clinical implications are discussed

    Shearwater Foraging in the Southern Ocean: The Roles of Prey Availability and Winds

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    Background Sooty (Puffinus griseus) and short-tailed (P. tenuirostris) shearwaters are abundant seabirds that range widely across global oceans. Understanding the foraging ecology of these species in the Southern Ocean is important for monitoring and ecosystem conservation and management. Methodology/Principal Findings Tracking data from sooty and short-tailed shearwaters from three regions of New Zealand and Australia were combined with at-sea observations of shearwaters in the Southern Ocean, physical oceanography, near-surface copepod distributions, pelagic trawl data, and synoptic near-surface winds. Shearwaters from all three regions foraged in the Polar Front zone, and showed particular overlap in the region around 140°E. Short-tailed shearwaters from South Australia also foraged in Antarctic waters south of the Polar Front. The spatial distribution of shearwater foraging effort in the Polar Front zone was matched by patterns in large-scale upwelling, primary production, and abundances of copepods and myctophid fish. Oceanic winds were found to be broad determinants of foraging distribution, and of the flight paths taken by the birds on long foraging trips to Antarctic waters. Conclusions/Significance The shearwaters displayed foraging site fidelity and overlap of foraging habitat between species and populations that may enhance their utility as indicators of Southern Ocean ecosystems. The results highlight the importance of upwellings due to interactions of the Antarctic Circumpolar Current with large-scale bottom topography, and the corresponding localised increases in the productivity of the Polar Front ecosystem

    Family Influences on the Long Term Post-Disaster Recovery of Puerto Rican Youth

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    This study focused on characteristics of the family environment that may mediate the relationship between disaster exposure and the presence of symptoms that met DSM-IV diagnostic criteria for symptom count and duration for an internalizing disorder in children and youth. We also explored how parental history of mental health problems may moderate this meditational model. Approximately 18 months after Hurricane Georges hit Puerto Rico in 1998, participants were randomly selected based on a probability household sample using 1990 US Census block groups. Caregivers and children (N=1,886 dyads) were interviewed with the Diagnostic Interview Schedule for Children and other questionnaires in Spanish. Areas of the family environment assessed include parent-child relationship quality, parent-child involvement, parental monitoring, discipline, parents’ relationship quality and parental mental health. SEM models were estimated for parents and children, and by age group. For children (4–10 years old), parenting variables were related to internalizing psychopathology, but did not mediate the exposure-psychopathology relationship. Exposure had a direct relationship to internalizing psychopathology. For youth (11–17 years old), some parenting variables attenuated the relation between exposure and internalizing psychopathology. Family environment factors may play a mediational role in psychopathology post-disaster among youth, compared to an additive role for children. Hurricane exposure had a significant relation to family environment for families without parental history of mental health problems, but no influence for families with a parental history of mental health problems

    Viral Evolution and Cytotoxic T Cell Restricted Selection in Acute Infant HIV-1 Infection

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    Antiretroviral therapy-naive HIV-1 infected infants experience poor viral containment and rapid disease progression compared to adults. Viral factors (e.g. transmitted cytotoxic T- lymphocyte (CTL) escape mutations) or infant factors (e.g. reduced CTL functional capacity) may explain this observation. We assessed CTL functionality by analysing selection in CTL-targeted HIV-1 epitopes following perinatal infection. HIV-1 gag, pol and nef sequences were generated from a historical repository of longitudinal specimens from 19 vertically infected infants. Evolutionary rate and selection were estimated for each gene and in CTL-restricted and non-restricted epitopes. Evolutionary rate was higher in nef and gag vs. pol, and lower in infants with non-severe immunosuppression vs. severe immunosuppression across gag and nef. Selection pressure was stronger in infants with non-severe immunosuppression vs. severe immunosuppression across gag. The analysis also showed that infants with non-severe immunosuppression had stronger selection in CTL-restricted vs. non-restricted epitopes in gag and nef. Evidence of stronger CTL selection was absent in infants with severe immunosuppression. These data indicate that infant CTLs can exert selection pressure on gag and nef epitopes in early infection and that stronger selection across CTL epitopes is associated with favourable clinical outcomes. These results have implications for the development of paediatric HIV-1 vaccines

    Systematic Mutational Analysis of the Intracellular Regions of Yeast Gap1 Permease

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    The yeast general amino acid permease Gap1 is a convenient model for studying the intracellular trafficking of membrane proteins. Present at the plasma membrane when the nitrogen source is poor, it undergoes ubiquitin-dependent endocytosis and degradation upon addition of a good nitrogen source, e.g. ammonium. It comprises 12 transmembrane domains (TM) flanked by cytosol-facing N- and C-terminal tails (NT, CT). The NT of Gap1 contains the acceptor lysines for ubiquitylation and its CT includes a sequence essential to exit from the endoplasmic reticulum (ER).Journal ArticleResearch Support, Non-U.S. Gov'tSCOPUS: ar.jinfo:eu-repo/semantics/publishe

    Associations between DSM-IV diagnosis, psychiatric symptoms and morning cortisol levels in a community sample of adolescents

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    Purpose. Dysfunction of the hypothalamic-pituitary-adrenocortical axis (HPA-axis) is implicated in a variety of psychiatric and emotional disorders. In this study, we explore the association between HPA-axis functioning, as measured by morning cortisol, and common psychiatric disorders and symptoms among a community sample of adolescents. Method. Data from a cross-sectional school-based survey of 501 school pupils, aged 15, were used to establish the strength of association between salivary morning cortisol and both diagnosis of psychiatric disorders and a number of psychiatric symptoms, as measured via a computerised psychiatric interview. Analysis, conducted separately by gender, used multiple regressions, adjusting for relevant confounders. Results-á-áWith one exception (a positive association between conduct disorder symptoms and cortisol among females) there was no association between morning cortisol and psychiatric diagnosis or symptoms. However, there was a significant two-way interaction between gender and conduct symptoms, with females showing a positive and males a negative association between cortisol and conduct symptoms. A further three-way interaction showed that while the association between cortisol and conduct symptoms was negative among males with a few mood disorder symptoms, among females with many mood symptoms it was positive. Conclusions. Except in relation to conduct symptoms, dysregulation of morning cortisol levels seems unrelated to any psychiatric disorder or symptoms. However, the relationship between cortisol and conduct symptoms is moderated by both gender and mood symptoms. Findings are compatible with the recent work suggesting research should concentrate on the moderated associations between gender, internalising and externalising symptoms and cortisol, rather than any simple relationship

    Imaginal Discs – A New Source of Chromosomes for Genome Mapping of the Yellow Fever Mosquito Aedes aegypti

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    Dengue fever is an emerging health threat to as much as half of the human population around the world. No vaccines or drug treatments are currently available. Thus, disease prevention is largely based on efforts to control its major mosquito vector Ae. aegypti. Novel vector control strategies, such as population replacement with pathogen-incompetent transgenic mosquitoes, rely on detailed knowledge of the genome organization for the mosquito. However, the current genome assembly of Ae. aegypti is highly fragmented and requires additional physical mapping onto chromosomes. The absence of readable polytene chromosomes makes genome mapping for this mosquito extremely challenging. In this study, we discovered and investigated a new source of chromosomes useful for the cytogenetic analysis in Ae. aegypti – mitotic chromosomes from imaginal discs of 4th instar larvae. Using natural banding patterns of these chromosomes, we developed a new band-based approach for physical mapping of DNA probes to the precise chromosomal positions. Further application of this approach for genome mapping will greatly enhance the utility of the existing draft genome sequence assembly for Ae. aegypti and thereby facilitate application of advanced genome technologies for investigating and developing novel genetic control strategies for dengue transmission
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