221 research outputs found

    Easy on that trigger dad: a study of long term family photo retrieval

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    We examine the effects of new technologies for digital photography on people's longer term storage and access to collections of personal photos. We report an empirical study of parents' ability to retrieve photos related to salient family events from more than a year ago. Performance was relatively poor with people failing to find almost 40% of pictures. We analyze participants' organizational and access strategies to identify reasons for this poor performance. Possible reasons for retrieval failure include: storing too many pictures, rudimentary organization, use of multiple storage systems, failure to maintain collections and participants' false beliefs about their ability to access photos. We conclude by exploring the technical and theoretical implications of these findings

    The crystal structure of human Rogdi provides insight into the causes of Kohlschutter-Tonz Syndrome

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    Kohlschutter-Tönz syndrome (KTS) is a rare autosomal-recessive disorder of childhood onset characterized by global developmental delay, spasticity, epilepsy, and amelogenesis imperfecta. Rogdi, an essential protein, is highly conserved across metazoans, and mutations in Rogdi are linked to KTS. However, how certain mutations in Rogdi abolish its physiological functions and cause KTS is not known. In this study, we determined the crystal structure of human Rogdi protein at atomic resolution. Rogdi forms a novel elongated curved structure comprising the ?? domain, a leucine-zipper-like four-helix bundle, and a characteristic ??-sheet domain. Within the ?? domain, the N-terminal H1 helix (residues 19-45) pairs with the C-terminal H6 helix (residues 252-287) in an antiparallel manner, indicating that the integrity of the four-helix bundle requires both N- and C-terminal residues. The crystal structure, in conjunction with biochemical data, indicates that the ?? domain might undergo a conformational change and provide a structural platform for protein-protein interactions. Disruption of the four-helix bundle by mutation results in significant destabilization of the structure. This study provides structural insights into how certain mutations in Rogdi affect its structure and cause KTS, which has important implications for the development of pharmaceutical agents against this debilitating neurological disease

    Clinical features of children and adults with a muscular dystrophy using powered indoor/outdoor wheelchairs (EPIOCs): disease features, comorbidities and complications of disability.

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    Purpose: To describe the clinical features of electric powered indoor/outdoor wheelchair users with a muscular dystrophy, likely to influence optimal prescription; reflecting features of muscular dystrophies, conditions secondary to disability and comorbidities impacting on equipment provision. Methods: cross-sectional retrospective case note review of recipients of electric powered indoor/outdoor wheelchairs provided by a specialist regional wheelchair service. Data on demography, diagnostic/clinical and wheelchair prescription were systematically extracted. Results: Fifty-one men and 14 women, mean age 23.7 (range 10-67, sd 12.95) years, were studied. Forty had Duchenne muscular dystrophy, 22 had other forms of muscular dystrophy and three were unclassified. Twenty-seven were aged under 19. Notable clinical features included problematic pain (10), cardiomyopathy (5) and ventilatory failure (4). Features related to disability were (kypho)scoliosis (20) and oedema/cellulitis (3) whilst comorbidities included back pain (5). Comparison of younger with older users revealed younger users had more features of muscular dystrophy affecting electric powered chair provision (56%) whilst older users had more comorbidity (37%). Tilt-in-space was prescribed for 81% of users, specialised seating for 55% and complex controls for 16%. Conclusions: Muscular dystrophy users were prescribed electric powered indoor/outdoor chairs with many additional features reflecting the consequences of profound muscle weakness. In addition to facilitating independence and participation, electric powered indoor/outdoor chairs have major therapeutic benefits

    Mid-circuit qubit measurement and rearrangement in a 171^{171}Yb atomic array

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    Measurement-based quantum error correction relies on the ability to determine the state of a subset of qubits (ancillae) within a processor without revealing or disturbing the state of the remaining qubits. Among neutral-atom based platforms, a scalable, high-fidelity approach to mid-circuit measurement that retains the ancilla qubits in a state suitable for future operations has not yet been demonstrated. In this work, we perform imaging using a narrow-linewidth transition in an array of tweezer-confined 171^{171}Yb atoms to demonstrate nondestructive state-selective and site-selective detection. By applying site-specific light shifts, selected atoms within the array can be hidden from imaging light, which allows a subset of qubits to be measured while causing only percent-level errors on the remaining qubits. As a proof-of-principle demonstration of conditional operations based on the results of the mid-circuit measurements, and of our ability to reuse ancilla qubits, we perform conditional refilling of ancilla sites to correct for occasional atom loss, while maintaining the coherence of data qubits. Looking towards true continuous operation, we demonstrate loading of a magneto-optical trap with a minimal degree of qubit decoherence.Comment: 9 pages, 6 figure

    Disclosure of cholesterol recognition motifs in transmembrane domains of the human nicotinic acetylcholine receptor

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    Cholesterol influences ion-channel function, distribution and clustering in the membrane, endocytosis, and exocytic sorting of the nicotinic acetylcholine receptor (AChR). We report the occurrence of a cholesterol recognition motif, here coined “CARC”, in the transmembrane regions of AChR subunits that bear extensive contact with the surrounding lipid, and are thus optimally suited to convey cholesterol-mediated signaling from the latter. Three cholesterol molecules could be docked on the transmembrane segments of each AChR subunit, rendering a total of 15 cholesterol molecules per AChR molecule. The CARC motifs contribute each with an energy of interaction between 35 and 52 kJ.mol−1, adding up to a total of about 200 kJ.mol−1 per receptor molecule, i.e. ∼40% of the lipid solvation free energy/ AChR molecule. The CARC motif is remarkably conserved along the phylogenetic scale, from prokaryotes to human, suggesting that it could be responsible for some of the above structural/functional properties of the AChR

    Apolipophorin-III Mediates Antiplasmodial Epithelial Responses in Anopheles gambiae (G3) Mosquitoes

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    Apolipophorin-III (ApoLp-III) is known to play an important role in lipid transport and innate immunity in lepidopteran insects. However, there is no evidence of involvement of ApoLp-IIIs in the immune responses of dipteran insects such as Drosophila and mosquitoes.We report the molecular and functional characterization of An. gambiae apolipophorin-III (AgApoLp-III). Mosquito ApoLp-IIIs have diverged extensively from those of lepidopteran insects; however, the predicted tertiary structure of AgApoLp-III is similar to that of Manduca sexta (tobacco hornworm). We found that AgApoLp-III mRNA expression is strongly induced in the midgut of An. gambiae (G3 strain) mosquitoes in response to Plasmodium berghei infection. Furthermore, immunofluorescence stainings revealed that high levels of AgApoLp-III protein accumulate in the cytoplasm of Plasmodium-invaded cells and AgApoLp-III silencing increases the intensity of P. berghei infection by five fold.There are broad differences in the midgut epithelial responses to Plasmodium invasion between An. gambiae strains. In the G3 strain of An. gambiae AgApoLp-III participates in midgut epithelial defense responses that limit Plasmodium infection

    Isolation, Characterization, and Stability of Discretely-Sized Nanolipoprotein Particles Assembled with Apolipophorin-III

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    Background: Nanolipoprotein particles (NLPs) are discoidal, nanometer-sized particles comprised of self-assembled phospholipid membranes and apolipoproteins. NLPs assembled with human apolipoproteins have been used for myriad biotechnology applications, including membrane protein solubilization, drug delivery, and diagnostic imaging. To expand the repertoire of lipoproteins for these applications, insect apolipophorin-III (apoLp-III) was evaluated for the ability to form discretely-sized, homogeneous, and stable NLPs. Methodology: Four NLP populations distinct with regards to particle diameters (ranging in size from 10 nm to.25 nm) and lipid-to-apoLp-III ratios were readily isolated to high purity by size exclusion chromatography. Remodeling of the purified NLP species over time at 4uC was monitored by native gel electrophoresis, size exclusion chromatography, and atomic force microscopy. Purified 20 nm NLPs displayed no remodeling and remained stable for over 1 year. Purified NLPs with 10 nm and 15 nm diameters ultimately remodeled into 20 nm NLPs over a period of months. Intra-particle chemical cross-linking of apoLp-III stabilized NLPs of all sizes. Conclusions: ApoLp-III-based NLPs can be readily prepared, purified, characterized, and stabilized, suggesting their utilit
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