2,131 research outputs found

    Severe underreporting of energy intake in normal weight subjects: use of an appropriate standard and relation to restrained eating

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    Abstract Objective: To assess the influence of different standards and restrained eating on underreporting in healthy, non-obese, weight-stable young subjects. Design and subjects: Eighty-three young adults (20-38 years, 55 women, 28 men) were assessed under weight-stable conditions with a 7-day dietary record and the three-factor eating questionnaire by Stunkard and Messick. Resting energy expenditure (REE; indirect calorimetry) plus data derived from physical activity records (PA) (Standard 1) or REE times an activity factor (AF) (Standard 2) was used as standard for total energy expenditure (TEE). For comparison, doubly labelled water (DLW) was used to measure TEE in a subgroup of subjects. Results: There was an association between self-reported energy intake and Standard 2 (r = 0.72) but not with Standard 1. When compared with DLW both calculated standards were inaccurate, but Standard 2 avoided high levels of overreporting. Using Standard 2 to identify ‘severe' underreporting (SU; as defined by a deviation of energy intake (EI) and TEE of >20%), SU was seen in 37% of all subjects. It was more frequently found in women than in men (49% of women, 14.3% of men, P < 0.05). Underreporting subjects had a reduced EI (P < 0.01) but there were no significant differences in nutritional status (body weight and height, body mass index, fat mass and fat-free mass), energy expenditure and the proportion of energy from macronutrients between normal and underreporting subjects. However, high restraint was associated with a higher degree of underreporting in the total group, whereas disinhibition had an influence only in men. Conclusions: A high prevalence of SU is seen in non-obese subjects. Characteristics of eating behaviour (restraint and disinhibition) were associated with underreporting but seemed to have a different influence in men and wome

    Boundaries of Disk-like Self-affine Tiles

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    Let T:=T(A,D)T:= T(A, {\mathcal D}) be a disk-like self-affine tile generated by an integral expanding matrix AA and a consecutive collinear digit set D{\mathcal D}, and let f(x)=x2+px+qf(x)=x^{2}+px+q be the characteristic polynomial of AA. In the paper, we identify the boundary T\partial T with a sofic system by constructing a neighbor graph and derive equivalent conditions for the pair (A,D)(A,{\mathcal D}) to be a number system. Moreover, by using the graph-directed construction and a device of pseudo-norm ω\omega, we find the generalized Hausdorff dimension dimHω(T)=2logρ(M)/logq\dim_H^{\omega} (\partial T)=2\log \rho(M)/\log |q| where ρ(M)\rho(M) is the spectral radius of certain contact matrix MM. Especially, when AA is a similarity, we obtain the standard Hausdorff dimension dimH(T)=2logρ/logq\dim_H (\partial T)=2\log \rho/\log |q| where ρ\rho is the largest positive zero of the cubic polynomial x3(p1)x2(qp)xqx^{3}-(|p|-1)x^{2}-(|q|-|p|)x-|q|, which is simpler than the known result.Comment: 26 pages, 11 figure

    Plasmacytoid dendritic cells orchestrate innate and adaptive anti-tumor immunity induced by oncolytic coxsackievirus A21

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    Background: The oncolytic virus, coxsackievirus A21 (CVA21), has shown promise as a single agent in several clinical trials and is now being tested in combination with immune checkpoint blockade. Combination therapies offer the best chance of disease control; however, the design of successful combination strategies requires a deeper understanding of the mechanisms underpinning CVA21 efficacy, in particular, the role of CVA21 anti-tumor immunity. Therefore, this study aimed to examine the ability of CVA21 to induce human anti-tumor immunity, and identify the cellular mechanism responsible. Methods: This study utilized peripheral blood mononuclear cells from i) healthy donors, ii) Acute Myeloid Leukemia (AML) patients, and iii) patients taking part in the STORM clinical trial, who received intravenous CVA21; patients receiving intravenous CVA21 were consented separately in accordance with local institutional ethics review and approval. Collectively, these blood samples were used to characterize the development of innate and adaptive anti-tumor immune responses following CVA21 treatment. Results: An Initial characterization of peripheral blood mononuclear cells, collected from cancer patients following intravenous infusion of CVA21, confirmed that CVA21 activated immune effector cells in patients. Next, using hematological disease models which were sensitive (Multiple Myeloma; MM) or resistant (AML) to CVA21-direct oncolysis, we demonstrated that CVA21 stimulated potent anti-tumor immune responses, including: 1) cytokine-mediated bystander killing; 2) enhanced natural killer cell-mediated cellular cytotoxicity; and 3) priming of tumor-specific cytotoxic T lymphocytes, with specificity towards known tumor-associated antigens. Importantly, immune-mediated killing of both MM and AML, despite AML cells being resistant to CVA21-direct oncolysis, was observed. Upon further examination of the cellular mechanisms responsible for CVA21-induced anti-tumor immunity we have identified the importance of type I IFN for NK cell activation, and demonstrated that both ICAM-1 and plasmacytoid dendritic cells were key mediators of this response. Conclusion: This work supports the development of CVA21 as an immunotherapeutic agent for the treatment of both AML and MM. Additionally, the data presented provides an important insight into the mechanisms of CVA21-mediated immunotherapy to aid the development of clinical biomarkers to predict response and rationalize future drug combinations

    The native architecture of a photosynthetic membrane

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    In photosynthesis, the harvesting of solar energy and its subsequent conversion into a stable charge separation are dependent upon an interconnected macromolecular network of membrane-associated chlorophyll–protein complexes. Although the detailed structure of each complex has been determined, the size and organization of this network are unknown. Here we show the use of atomic force microscopy to directly reveal a native bacterial photosynthetic membrane. This first view of any multi-component membrane shows the relative positions and associations of the photosynthetic complexes and reveals crucial new features of the organization of the network: we found that the membrane is divided into specialized domains each with a different network organization and in which one type of complex predominates. Two types of organization were found for the peripheral light-harvesting LH2 complex. In the first, groups of 10–20 molecules of LH2 form light-capture domains that interconnect linear arrays of dimers of core reaction centre (RC)–light-harvesting 1 (RC–LH1–PufX) complexes; in the second they were found outside these arrays in larger clusters. The LH1 complex is ideally positioned to function as an energy collection hub, temporarily storing it before transfer to the RC where photochemistry occurs: the elegant economy of the photosynthetic membrane is demonstrated by the close packing of these linear arrays, which are often only separated by narrow 'energy conduits' of LH2 just two or three complexes wide

    Reducing bias in auditory duration reproduction by integrating the reproduced signal

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    Duration estimation is known to be far from veridical and to differ for sensory estimates and motor reproduction. To investigate how these differential estimates are integrated for estimating or reproducing a duration and to examine sensorimotor biases in duration comparison and reproduction tasks, we compared estimation biases and variances among three different duration estimation tasks: perceptual comparison, motor reproduction, and auditory reproduction (i.e. a combined perceptual-motor task). We found consistent overestimation in both motor and perceptual-motor auditory reproduction tasks, and the least overestimation in the comparison task. More interestingly, compared to pure motor reproduction, the overestimation bias was reduced in the auditory reproduction task, due to the additional reproduced auditory signal. We further manipulated the signal-to-noise ratio (SNR) in the feedback/comparison tones to examine the changes in estimation biases and variances. Considering perceptual and motor biases as two independent components, we applied the reliability-based model, which successfully predicted the biases in auditory reproduction. Our findings thus provide behavioral evidence of how the brain combines motor and perceptual information together to reduce duration estimation biases and improve estimation reliability

    Substantial Seasonal Contribution of Observed Biogenic Sulfate Particles to Cloud Condensation Nuclei

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    Biogenic sources contribute to cloud condensation nuclei (CCN) in the clean marine atmosphere, but few measurements exist to constrain climate model simulations of their importance. The chemical composition of individual atmospheric aerosol particles showed two types of sulfate-containing particles in clean marine air masses in addition to mass-based Estimated Salt particles. Both types of sulfate particles lack combustion tracers and correlate, for some conditions, to atmospheric or seawater dimethyl sulfide (DMS) concentrations, which means their source was largely biogenic. The first type is identified as New Sulfate because their large sulfate mass fraction (63% sulfate) and association with entrainment conditions means they could have formed by nucleation in the free troposphere. The second type is Added Sulfate particles (38% sulfate), because they are preexisting particles onto which additional sulfate condensed. New Sulfate particles accounted for 31% (7 cm−3) and 33% (36 cm−3) CCN at 0.1% supersaturation in late-autumn and late-spring, respectively, whereas sea spray provided 55% (13 cm−3) in late-autumn but only 4% (4 cm−3) in late-spring. Our results show a clear seasonal difference in the marine CCN budget, which illustrates how important phytoplankton-produced DMS emissions are for CCN in the North Atlantic

    Exceptionally Preserved Cambrian Trilobite Digestive System Revealed in 3D by Synchrotron-Radiation X-Ray Tomographic Microscopy

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    The Cambrian ‘Orsten’ fauna comprises exceptionally preserved and phosphatised microscopic arthropods. The external morphology of these fossils is well known, but their internal soft-tissue anatomy has remained virtually unknown. Here, we report the first non-biomineralised tissues from a juvenile polymerid trilobite, represented by digestive structures, glands, and connective strands harboured in a hypostome from the Swedish ‘Orsten’ fauna. Synchrotron-radiation X-ray tomographic microscopy enabled three-dimensional internal recordings at sub-micrometre resolution. The specimen provides the first unambiguous evidence for a J-shaped anterior gut and the presence of a crop with a constricted alimentary tract in the Trilobita. Moreover, the gut is Y-shaped in cross section, probably due to a collapsed lumen of that shape, another feature which has not previously been observed in trilobites. The combination of anatomical features suggests that the trilobite hypostome is functionally analogous to the labrum of euarthropods and that it was a sophisticated element closely integrated with the digestive system. This study also briefly addresses the preservational bias of the ‘Orsten’ fauna, particularly the near-absence of polymerid trilobites, and the taphonomy of the soft-tissue-harbouring hypostome

    The control of attentional target selection in a colour/colour conjunction task

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    To investigate the time course of attentional object selection processes in visual search tasks where targets are defined by a combination of features from the same dimension, we measured the N2pc component as an electrophysiological marker of attentional object selection during colour/colour conjunction search. In Experiment 1, participants searched for targets defined by a combination of two colours, while ignoring distractor objects that matched only one of these colours. Reliable N2pc components were triggered by targets and also by partially matching distractors, even when these distractors were accompanied by a target in the same display. The target N2pc was initially equal in size to the sum of the two N2pc components to the two different types of partially matching distractors, and became superadditive from about 250 ms after search display onset. Experiment 2 demonstrated that the superadditivity of the target N2pc was not due to a selective disengagement of attention from task-irrelevant partially matching distractors. These results indicate that attention was initially deployed separately and in parallel to all target-matching colours, before attentional allocation processes became sensitive to the presence of both matching colours within the same object. They suggest that attention can be controlled simultaneously and independently by multiple features from the same dimension, and that feature-guided attentional selection processes operate in parallel for different target-matching objects in the visual field

    Antibody Engineering Using Phage Display with a Coiled-Coil Heterodimeric Fv Antibody Fragment

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    A Fab-like antibody binding unit, ccFv, in which a pair of heterodimeric coiled-coil domains was fused to VH and VL for Fv stabilization, was constructed for an anti-VEGF antibody. The anti-VEGF ccFv showed the same binding affinity as scFv but significantly improved stability and phage display level. Furthermore, phage display libraries in the ccFv format were constructed for humanization and affinity maturation of the anti-VEGF antibody. A panel of VH frameworks and VH-CDR3 variants, with a significant improvement in affinity and expressibility in both E. coli and yeast systems, was isolated from the ccFv phage libraries. These results demonstrate the potential application of the ccFv antibody format in antibody engineering
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