1,475 research outputs found

    Human preferences and risky choices

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    There are different views on what preferences for risks are and whether they are indicators of stable, underlying generic cognitive systems. Preferences could be conceived as an attitude towards a set of properties of context, memory and affect - a gauge of how much uncertainty one is willing to tolerate. This special issue aims to initiate a discussion on the stability of preferences for risks - as research has shown that different decision domains, response modes, and framing facilitate preference reversals. A consistent claim from behavioural decision researchers is that, contrary to the assumptions of classical economics, preferences are not stable and inherent constructs in individuals but are modified by levels of accessibility in memory, context, decision complexity, and type of psychological processing (e.g., sampling or computational “tradeoffs” in processing). For example, in a sampling-based decision-making paradigm it is argued that preferences are not essential for making risky decisions. The existing theoretical and empirical evidence reveals that human preferences are relative and unstable, undermining the predictions of normative theory. Recent theoretical accounts in psychology have expanded the debate further by offering evolutionary models of decision-making under risk. While most of the researcher has explored optimisation goals (traditionally assumed in economics), evolutionary psychology has promoted adaptation-driven processes for risky choices. Moreover, we have witnessed a renaissance of preferences as affect rather than as a construct with psycho-economical properties. Although behavioural decision research is still engaged in challenging the foundation of economic theory, at present, opinions seem less unified as to whether preferences reflect common psychological constructs

    Multiplexed Readout of Transmon Qubits with Josephson Bifurcation Amplifiers

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    Achieving individual qubit readout is a major challenge in the development of scalable superconducting quantum processors. We have implemented the multiplexed readout of a four transmon qubit circuit using non-linear resonators operated as Josephson bifurcation amplifiers. We demonstrate the simultaneous measurement of Rabi oscillations of the four transmons. We find that multiplexed Josephson bifurcation is a high-fidelity readout method, the scalability of which is not limited by the need of a large bandwidth nearly quantum-limited amplifier as is the case with linear readout resonators.Comment: 7 pages, 6 figures, and 31 reference

    Manipulating Fock states of a harmonic oscillator while preserving its linearity

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    We present a new scheme for controlling the quantum state of a harmonic oscillator by coupling it to an anharmonic multilevel system (MLS) with first to second excited state transition frequency on-resonance with the oscillator. In this scheme that we call "ef-resonant", the spurious oscillator Kerr non-linearity inherited from the MLS is very small, while its Fock states can still be selectively addressed via an MLS transition at a frequency that depends on the number of photons. We implement this concept in a circuit-QED setup with a microwave 3D cavity (the oscillator, with frequency 6.4 GHz and quality factor QO=2E-6) embedding a frequency tunable transmon qubit (the MLS). We characterize the system spectroscopically and demonstrate selective addressing of Fock states and a Kerr non-linearity below 350 Hz. At times much longer than the transmon coherence times, a non-linear cavity response with driving power is also observed and explained.Comment: 8 pages, 5 figure

    Deep exploration of a CDKN1C mutation causing a mixture of Beckwith-Wiedemann and IMAGe syndromes revealed a novel transcript associated with developmental delay

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    Background: Loss-of-function mutations in CDKN1C cause overgrowth, that is, Beckwith-Wiedemann syndrome (BWS), while gain-of-function variants in the gene’s PCNA binding motif cause a growth-restricted condition called IMAGe syndrome. We report on a boy with a remarkable mixture of both syndromes, with developmental delay and microcephaly as additional features. Methods: Whole-exome DNA sequencing and ultra-deep RNA sequencing of leucocyte-derived and fibroblast-derived mRNA were performed in the family. Results: We found a maternally inherited variant in the IMAGe hotspot region: NM_000076.2(CDKN1C) c.822_826delinsGAGCTG. The asymptomatic mother had inherited this variant from her mosaic father with mild BWS features. This delins caused tissue-specific frameshifting resulting in at least three novel mRNA transcripts in the boy. First, a splice product causing CDKN1C truncation was the likely cause of BWS. Second, an alternative splice product in fibroblasts encoded IMAGe-associated amino acid substitutions. Third, we speculate that developmental delay is caused by a change in the alternative CDKN1C-201 (ENST00000380725.1) transcript, encoding a novel isoform we call D (UniProtKB: A6NK88). Isoform D is distinguished from isoforms A and B by alternative splicing within exon 1 that changes the reading frame of the last coding exon. Remarkably, this delins changed the reading frame back to the isoform A/B type, resulting in a hybrid D–A/B isoform. Conclusion: Three different cell-type-dependent RNA products can explain the co-occurrence of both BWS and IMAGe features in the boy. Possibly, brain expression of hybrid isoform D–A/B is the cause of developmental delay and microcephaly, a phenotypic feature not previously reported in CDKN1C patients.publishedVersio

    Lenalidomide monotherapy and in combination with cytarabine, daunorubicin and etoposide for high-risk myelodysplasia and acute myeloid leukaemia with chromosome 5 abnormalities

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    Patients with high risk myelodysplasia (HR-MDS) and acute myeloid leukaemia (AML) with chromosomal changes involving deletion of the long arm of chromosome 5 (del5q), especially with complex karyotype, rarely have a durable response to combination chemotherapy. In the subgroup with monosomal karyotype there are no long term survivors (Fang et al., 2011) [1]. Recent experience indicates that the incidence of del5q in AML is ~20-30%, with only 20-25% of patients achieving complete remission (CR) (Farag et al., 2006) [2]. Additionally, therapy has significant toxicity, with induction death rates ~20% even in younger patients (Juliusson et al., 2009) [3]. This lack of efficacy provides the clinical rationale for combination/sequential therapy with Lenalidomide and combination chemotherapy. Dose dependent haematological toxicity is the major safety concern with such a combination protocol. Therefore we conducted a phase 2 study, AML Len5 (ISRCTN58492795), to assess safety, tolerability and efficacy of lenalidomide monotherapy, followed by lenalidomide with intensive chemotherapy in patients with primary/relapsed/refractory high risk MDS or AML with abnormalities of chromosome 5. © 2013 The Authors

    Diagnostic imaging in adult non-cystic fibrosis bronchiectasis.

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    To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked DownloadRadiology plays a key role in the diagnosis of bronchiectasis, defined as permanent dilatation of the bronchial lumen. Volumetric thin-section multidetector computed tomography is an excellent noninvasive modality to evaluate bronchiectasis. Bronchiectasis is categorised by morphological appearance. Cylindrical bronchiectasis has a smooth tubular configuration and is the most common form. Varicose bronchiectasis has irregular contours with alternating dilating and contracting lumen. Cystic bronchiectasis is the most severe form and exhibits saccular dilatation of bronchi. Bronchial dilatation is the hallmark of bronchiectasis and is evaluated in relation to the accompanying pulmonary artery. A broncho-arterial ratio exceeding 1:1 should be considered abnormal. Normal bronchi are narrower in diameter the further they are from the lung hila. Lack of normal bronchial tapering over 2 cm in length, distal from an airway bifurcation, is the most sensitive sign of bronchiectasis. Findings commonly associated with bronchiectasis include bronchial wall thickening, mucus plugging and tree-in-bud opacities. Bronchiectasis results from a myriad of conditions, with post-infectious bronchiectasis being the most common. Imaging can sometimes discern the cause of bronchiectasis. However, in most cases it is nonspecific or only suggestive of aetiology. While morphological types are nonspecific, the distribution of abnormality offers clues to aetiology. KEY POINTS: Bronchiectasis is a chronic progressive condition with significant disease burden and frequent exacerbations, for which the diagnosis relies on cross-sectional imaging.The major imaging findings include bronchial dilatation, bronchial contour abnormalities and visualisation of the normally invisible peripheral airways.Bronchiectasis is the end result of various conditions, including immunodeficiencies, mucociliary disorders and infections. Imaging is often nonspecific with regard to aetiology but can be suggestive.Distribution of abnormality in the lung offers helpful clues for establishing aetiology. EDUCATIONAL AIMS: To review the cross-sectional imaging appearance of bronchiectasis and the common associated findings.To get a sense of how radiology can aid in establishing the aetiology of bronchiectasis

    Polysomnographic comparison of sleep in children with obesity and normal weight without suspected sleep-related breathing disorder

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    Short sleep and obstructive apneas/hypopneas have been shown to be associated with childhood obesity. Still, few studies have compared sleep in children with obesity, without suspected sleep disordered breathing and normal weight peers by objective sleep measures and compared results with subjective parent assessment of sleep. Children with obesity aged 7–13 years (N = 44) and a matched group of normal weight children (N = 42) completed clinical polysomnography (Embla A10 Recording System). Parents scored their children's sleep on the Children's Sleep Habits Questionnaire (CSHQ). Mann–Whitney U tests were used to compare groups. There was a higher obstructive apnea/hypopnea index (AHI) (median obesity = 1.20 vs. median normal = 0.66; z = −1.33, U = 560.50, p = 0.002) and number of oxygen desaturation events per hour (median obesity = 0.7 vs. median normal = 0.2; z = −3.45, U = 402.50, p = 0.001) in the children with obesity compared to children with normal weight. The children with obesity had a significantly longer sleep duration (median obesity 8:50 h = vs. median normal = 8:32 h; z = −2.05, U = 687.00, p = 0.041), longer stage N2 sleep (median obesity = 87 min vs. median normal = 52 min; z = −2.87, U = 576.50, p = 0. 004) and shorter REM sleep (median obesity = 94 min vs. median normal = 121 min; z = 5.05, U = 1477.00, p ≤ .001). No differences were observed for time in sleep stage N1 and N3, wake time after sleep onset or the total arousal index . Further, no group differences were found on the CSHQ sleep-disordered breathing sub-scale (p = 0.399). The children with obesity demonstrated significantly more mild to moderate sleep disordered breathing than children with normal weight, although this was not corroborated by parent report.publishedVersio

    Reduction Resistant and Rigid Nitroxide Spin-Labels for DNA and RNA

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    Post-print (lokagerð höfundar)Electron paramagnetic resonance (EPR) spectroscopy, coupled with site-directed spin labeling (SDSL), is a useful method for studying conformational changes of biomolecules in cells. To employ in-cell EPR using nitroxide-based spin labels, the structure of the nitroxides must confer reduction resistance to withstand the reductive environment within cells. Here, we report the synthesis of two new spin labels, EÇ and EÇm, both of which possess the rigidity and the reduction resistance needed for extracting detailed structural information by EPR spectroscopy. EÇ and EÇm were incorporated into DNA and RNA, respectively, by oligonucleotide synthesis. Both labels were shown to be nonperturbing of the duplex structure. The partial reduction of EÇm during RNA synthesis was circumvented by the protection of the nitroxide as a benzoylated hydroxylamine.The authors acknowledge financial support from the Icelandic Research Fund (173727-051). The authors thank Dr. S. Jonsdottir for assistance with collecting analytical data for structural characterization of new compounds and members of the Sigurdsson research group for helpful discussions.Peer reviewe

    Nitroxide‐Derived N‐Oxide Phenazines for Noncovalent Spin‐Labeling of DNA

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    Post-print (lokagerð höfundar)Two o‐benzoquinone derivatives of isoindoline were synthesized for use as building blocks to incorporate isoindoline nitroxides into different compounds and materials. These o‐quinones were condensed with a number of o‐phenylenediamines to form isoindoline‐phenazines in high yields. Subsequent oxidation gave phenazine‐di‐N‐oxide isoindoline nitroxides that were evaluated for noncovalent and site‐directed spin‐labeling of duplex DNA and RNA that contained abasic sites. Although only minor binding was observed for RNA, the unsubstituted phenazine‐N,N‐dioxide tetramethyl isoindoline nitroxide showed high binding affinity and selectivity towards abasic sites in duplex DNA that contained cytosine as the orphan base.The authors acknowledge financial support from the Icelandic Research Fund (173727-051). The authors thank Dr S. Jonsdottir for assistance with collecting analytical data for structural characterization of new compounds, Dr. Thomas Halbritter for critically reading this manuscript, and the members of the Sigurdsson research group for helpful discussions.Peer reviewe
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