237 research outputs found
Lattice Boltzmann simulations of soft matter systems
This article concerns numerical simulations of the dynamics of particles
immersed in a continuum solvent. As prototypical systems, we consider colloidal
dispersions of spherical particles and solutions of uncharged polymers. After a
brief explanation of the concept of hydrodynamic interactions, we give a
general overview over the various simulation methods that have been developed
to cope with the resulting computational problems. We then focus on the
approach we have developed, which couples a system of particles to a lattice
Boltzmann model representing the solvent degrees of freedom. The standard D3Q19
lattice Boltzmann model is derived and explained in depth, followed by a
detailed discussion of complementary methods for the coupling of solvent and
solute. Colloidal dispersions are best described in terms of extended particles
with appropriate boundary conditions at the surfaces, while particles with
internal degrees of freedom are easier to simulate as an arrangement of mass
points with frictional coupling to the solvent. In both cases, particular care
has been taken to simulate thermal fluctuations in a consistent way. The
usefulness of this methodology is illustrated by studies from our own research,
where the dynamics of colloidal and polymeric systems has been investigated in
both equilibrium and nonequilibrium situations.Comment: Review article, submitted to Advances in Polymer Science. 16 figures,
76 page
Large introns in relation to alternative splicing and gene evolution: a case study of Drosophila bruno-3
Background:
Alternative splicing (AS) of maturing mRNA can generate structurally and functionally distinct transcripts from the same gene. Recent bioinformatic analyses of available genome databases inferred a positive correlation between intron length and AS. To study the interplay between intron length and AS empirically and in more detail, we analyzed the diversity of alternatively spliced transcripts (ASTs) in the Drosophila RNA-binding Bruno-3 (Bru-3) gene. This gene was known to encode thirteen exons separated by introns of diverse sizes, ranging from 71 to 41,973 nucleotides in D. melanogaster. Although Bru-3's structure is expected to be conducive to AS, only two ASTs of this gene were previously described.
Results:
Cloning of RT-PCR products of the entire ORF from four species representing three diverged Drosophila lineages provided an evolutionary perspective, high sensitivity, and long-range contiguity of splice choices currently unattainable by high-throughput methods. Consequently, we identified three new exons, a new exon fragment and thirty-three previously unknown ASTs of Bru-3. All exon-skipping events in the gene were mapped to the exons surrounded by introns of at least 800 nucleotides, whereas exons split by introns of less than 250 nucleotides were always spliced contiguously in mRNA. Cases of exon loss and creation during Bru-3 evolution in Drosophila were also localized within large introns. Notably, we identified a true de novo exon gain: exon 8 was created along the lineage of the obscura group from intronic sequence between cryptic splice sites conserved among all Drosophila species surveyed. Exon 8 was included in mature mRNA by the species representing all the major branches of the obscura group. To our knowledge, the origin of exon 8 is the first documented case of exonization of intronic sequence outside vertebrates.
Conclusion:
We found that large introns can promote AS via exon-skipping and exon turnover during evolution likely due to frequent errors in their removal from maturing mRNA. Large introns could be a reservoir of genetic diversity, because they have a greater number of mutable sites than short introns. Taken together, gene structure can constrain and/or promote gene evolution
Towards Quantum Repeaters with Solid-State Qubits: Spin-Photon Entanglement Generation using Self-Assembled Quantum Dots
In this chapter we review the use of spins in optically-active InAs quantum
dots as the key physical building block for constructing a quantum repeater,
with a particular focus on recent results demonstrating entanglement between a
quantum memory (electron spin qubit) and a flying qubit (polarization- or
frequency-encoded photonic qubit). This is a first step towards demonstrating
entanglement between distant quantum memories (realized with quantum dots),
which in turn is a milestone in the roadmap for building a functional quantum
repeater. We also place this experimental work in context by providing an
overview of quantum repeaters, their potential uses, and the challenges in
implementing them.Comment: 51 pages. Expanded version of a chapter to appear in "Engineering the
Atom-Photon Interaction" (Springer-Verlag, 2015; eds. A. Predojevic and M. W.
Mitchell
What orthopaedic surgery residents need to know about the hand and wrist?
<p>Abstract</p> <p>Background</p> <p>To develop a Core Curriculum for Orthopaedic Surgery; and to conduct a national survey to assess the importance of curriculum items as judged by orthopaedic surgeons with primary affiliation non-academic. Attention for this manuscript was focused on determining the importance of topics pertaining to adult hand and wrist reconstruction.</p> <p>Methods</p> <p>A 281-item questionnaire was developed and consisted of three sections: 1) Validated Musculoskeletal Core Curriculum; 2) Royal College of Physician and Surgeons of Canada (RCPSC) Specialty Objectives and; 3) A procedure list. A random group of 131 [out of 156] orthopaedic surgeons completed the questionnaire. Data were analyzed descriptively and quantitatively using histograms, a Modified Hotel ling's T<sup>2</sup>-statistic <abbrgrp><abbr bid="B1">1</abbr></abbrgrp> with p-value determined by a permutation test, and the Benjamini-Hochberg/Yekutieli procedure</p> <p>Results</p> <p>131/156 (84%) orthopaedic surgeons participated in this study. 27/32 items received an average mean score of at least 3.0/4.0 by all respondents thus suggesting that 84% of the items are either "probably important" or "important" to know by the end of residency (SD range 0.007–0.228). The Benjamini-Hochberg procedure demonstrated that for 80% of the 32 × 31/2 = 496 possible pairs of hand and wrist questions did not appear to demonstrate the same distribution of ratings given that one question was different from that of another question.</p> <p>Conclusion</p> <p>This study demonstrates with reliable statistical evidence, agreement on the importance of 27/32 items pertaining to hand and wrist reconstruction is included in a Core Curriculum for Orthopaedic Surgery. Residency training programs need ensure that educational opportunities focusing on the ability to perform with proficiency procedures pertaining to the hand and wrist is taught and evaluated in their respective programs.</p
Social Networks and Friendships at School: Comparing Children With and Without ASD
Self, peer and teacher reports of social relationships were examined for 60 high-functioning children with ASD. Compared to a matched sample of typical children in the same classroom, children with ASD were more often on the periphery of their social networks, reported poorer quality friendships and had fewer reciprocal friendships. On the playground, children with ASD were mostly unengaged but playground engagement was not associated with peer, self, or teacher reports of social behavior. Twenty percent of children with ASD had a reciprocated friendship and also high social network status. Thus, while the majority of high functioning children with ASD struggle with peer relationships in general education classrooms, a small percentage of them appear to have social success
Follow-up of atheroma burden with sequential whole body contrast enhanced MR angiography:a feasibility study
Assess the feasibility of whole body magnetic resonance angiography (WB-MRA) for monitoring global atheroma burden in a population with peripheral arterial disease (PAD). 50 consecutive patients with symptomatic PAD referred for clinically indicated MRA were recruited. Whole body MRA (WB-MRA) was performed at baseline, 6 months and 3 years. The vasculature was split into 31 anatomical arterial segments. Each segment was scored according to degree of luminal narrowing: 0 = normal, 1 = <50 %, 2 = 50–70 %, 3 = 71–99 %, 4 = vessel occlusion. The score from all assessable segments was summed, and then normalised to the number of assessable vessels. This normalised score was divided by four (the maximum vessel score) and multiplied by 100 to give a final standardised atheroma score (SAS) with a score of 0–100. Progression was assessed with repeat measure ANOVA. 36 patients were scanned at 0 and 6 months, with 26 patients scanned at the 3 years follow up. Only those who completed all three visits were included in the final analysis. Baseline atherosclerotic burden was high with a mean SAS of 15.7 ± 10.3. No significant progression was present at 6 months (mean SAS 16.4 ± 10.5, p = 0.67), however there was significant disease progression at 3 years (mean SAS 17.7 ± 11.5, p = 0.01). Those with atheroma progression at follow-up were less likely to be on statin therapy (79 vs 100 %, p = 0.04), and had significantly higher baseline SAS (17.6 ± 11.2 vs 10.7 ± 5.1, p = 0.043). Follow up of atheroma burden is possible with WB-MRA, which can successfully quantify and monitor atherosclerosis progression at 3 years follow-up
The CUGBP2 Splicing Factor Regulates an Ensemble of Branchpoints from Perimeter Binding Sites with Implications for Autoregulation
Alternative pre-mRNA splicing adjusts the transcriptional output of the genome by generating related mRNAs from a single primary transcript, thereby expanding protein diversity. A fundamental unanswered question is how splicing factors achieve specificity in the selection of target substrates despite the recognition of information-poor sequence motifs. The CUGBP2 splicing regulator plays a key role in the brain region-specific silencing of the NI exon of the NMDA R1 receptor. However, the sequence motifs utilized by this factor for specific target exon selection and its role in splicing silencing are not understood. Here, we use chemical modification footprinting to map the contact sites of CUGBP2 to GU-rich motifs closely positioned at the boundaries of the branch sites of the NI exon, and we demonstrate a mechanistic role for this specific arrangement of motifs for the regulation of branchpoint formation. General support for a branch site-perimeter–binding model is indicated by the identification of a group of novel target exons with a similar configuration of motifs that are silenced by CUGBP2. These results reveal an autoregulatory role for CUGBP2 as indicated by its direct interaction with functionally significant RNA motifs surrounding the branch sites upstream of exon 6 of the CUGBP2 transcript itself. The perimeter-binding model explains how CUGBP2 can effectively embrace the branch site region to achieve the specificity needed for the selection of exon targets and the fine-tuning of alternative splicing patterns
Responsibility Ascriptions in Technology Development and Engineering: Three Perspectives
In the last decades increasing attention is paid to the topic of responsibility in technology development and engineering. The discussion of this topic is often guided by questions related to liability and blameworthiness. Recent discussions in engineering ethics call for a reconsideration of the traditional quest for responsibility. Rather than on alleged wrongdoing and blaming, the focus should shift to more socially responsible engineering, some authors argue. The present paper aims at exploring the different approaches to responsibility in order to see which one is most appropriate to apply to engineering and technology development. Using the example of the development of a new sewage water treatment technology, the paper shows how different approaches for ascribing responsibilities have different implications for engineering practice in general, and R&D or technological design in particular. It was found that there was a tension between the demands that follow from these different approaches, most notably between efficacy and fairness. Although the consequentialist approach with its efficacy criterion turned out to be most powerful, it was also shown that the fairness of responsibility ascriptions should somehow be taken into account. It is proposed to look for alternative, more procedural ways to approach the fairness of responsibility ascriptions
Cohort comparison study of cardiac disease and atherosclerotic burden in type 2 diabetic adults using whole body cardiovascular magnetic resonance imaging
BACKGROUND: Whole body cardiovascular MR (WB CVMR) combines whole body angiography and cardiac MR assessment. It is accepted that there is a high disease burden in patients with diabetes, however the quantification of the whole body atheroma burden in both arterial and cardiac disease has not been previously reported. In this study we compare the quantified atheroma burden in those individuals with and without diabetes by clinical cardiovascular disease (CVD) status. METHODS: 158 participants underwent WB CVMR, and were categorised into one of four groups: (1) type 2 diabetes mellitus (T2DM) with CVD; (2) T2DM without CVD; (3) CVD without T2DM; (4) healthy controls. The arterial tree was subdivided into 31 segments and each scored according to the degree of stenosis. From this a standardised atheroma score (SAS) was calculated. Cardiac MR and late gadolinium enhancement images of the left ventricle were obtained for assessment of mass, volume and myocardial scar assessment. RESULTS: 148 participants completed the study protocol—61 % male, with mean age of 64 ± 8.2 years. SAS was highest in those with cardiovascular disease without diabetes [10.1 (0–39.5)], followed by those with T2DM and CVD [4 (0–41.1)], then those with T2DM only [3.23 (0–19.4)] with healthy controls having the lowest atheroma score [2.4 (0–19.4)]. Both groups with a prior history of CVD had a higher SAS and left ventricular mass than those without (p < 0.001 for both). However after accounting for known cardiovascular risk factors, only the SAS in the group with CVD without T2DM remained significantly elevated. 6 % of the T2DM group had evidence of silent myocardial infarct, with this subcohort having a higher SAS than the remainder of the T2DM group [7.7 (4–19) vs. 2.8 (0–17), p = 0.024]. CONCLUSIONS: Global atheroma burden was significantly higher in those with known cardiovascular disease and without diabetes but not in those with diabetes and cardiovascular disease suggesting that cardiovascular events may occur at a lower atheroma burden in diabetes. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12933-015-0284-2) contains supplementary material, which is available to authorized users
Parental alcohol use and adolescent school adjustment in the general population: Results from the HUNT study
<p>Abstract</p> <p>Background</p> <p>This study investigates the relationship between parental drinking and school adjustment in a total population sample of adolescents, with independent reports from mothers, fathers, and adolescents. As a group, children of alcohol abusers have previously been found to exhibit lowered academic achievement. However, few studies address which parts of school adjustment that may be impaired. Both a genetic approach and social strains predict elevated problem scores in these children. Previous research has had limitations such as only recruiting cases from clinics, relying on single responders for all measures, or incomplete control for comorbid psychopathology. The specific effects of maternal and paternal alcohol use are also understudied.</p> <p>Methods</p> <p>In a Norwegian county, 88% of the population aged 13-19 years participated in a health survey (N = 8984). Among other variables, adolescents reported on four dimensions of school adjustment, while mothers and fathers reported their own drinking behaviour. Mental distress and other control variables were adjusted for. Multivariate analysis including generalized estimation equations was applied to investigate associations.</p> <p>Results</p> <p>Compared to children of light drinkers, children of alcohol abusers had moderately elevated attention and conduct problem scores. Maternal alcohol abuse was particularly predictive of such problems. Children of abstainers did significantly better than children of light drinkers. Controlling for adolescent mental distress reduced the association between maternal abuse and attention problems. The associations between parental reported drinking and school adjustment were further reduced when controlling for the children's report of seeing their parents drunk, which itself predicted school adjustment. Controlling for parental mental distress did not reduce the associations.</p> <p>Conclusions</p> <p>Parental alcohol abuse is an independent risk factor for attention and conduct problems at school. Some of the risk associated with mothers' drinking is likely to be mediated by adolescent mental distress. Despite lowered adjustment on the externalizing dimensions, children of alcohol abusers report that they enjoy being at school as much as other children.</p
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