158 research outputs found

    Computer-assisted pre-operative automatic segmentation and registration tool for malunited radius osteotomy: A proof-of-concept study

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    Corrective osteotomy is a standard treatment for distal radius fractures in malunited radius cases. In order to increase the efficiency of the osteotomy pre-operative plan, in this study, a proof-of-concept framework of automatic computer-assisted segmentation and registration tool was developed for the purpose of malunited radius osteotomy pre-operative planning. The program consisted of the functions of segmentation, virtual cutting, automatic alignment and registration. One computed tomography (CT) scanning dataset of a patient's bilateral forearm was employed as an illustration example in this study. Three templates of 3D models including the healthy radius, and the pre- and post-correction injured radius were output as STL geometries for pre-operative plan purposes

    The quiet editor: Ivan Vladislavić and South African cultural production

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    This article examines the literary and sociological significance of Ivan Vladislavić’s "double life” (Lahire, 2010: n.p.) as both editor and writer. With reference to a number of his editorial roles as well as the joint projects he has worked on with writers and visual artists, the article considers how Vladislavić’s work with others spreads symbolic value. Described by one of his clients as the “quiet editor”, Vladislavić can be read as a new kind of author; what he terms “creative editing” (Steyn, 2012: n.p.) as a new kind of writing, through which more traditional models of authorship and literary production are thrown into question — less Bourdieu’s (1984) “field of literary production” or Casanova’s (2004: 82) “world literary space”, red in tooth and claw, amd more Howard Becker’s “art world”: a convivial “network of cooperating people, all of whose work is essential to the final outcome” (1982: 25)

    Dynorphin knockout reduces fat mass and increases weight loss during fasting in mice

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    Endogenous opioids, particularly dynorphins, have been implicated in regulation of energy balance, but it is not known how they mediate this in vivo. We investigated energy homeostasis in dynorphin knockout mice (Dyn -/- mice) and probed the interactions between dynorphins and the neuropeptide Y (NPY) system. Dyn-/- mice were no different from wild types with regards to body weight and basal and fasting-induced food intake, but fecal output was increased, suggesting decreased nutrient absorption, and they had significantly less white fat and lost more weight during a 24-h fast. The neuroendocrine and thermal responses to fasting were at least as pronounced in Dyn-/- as in wild types, and there was no stimulatory effect of dynorphin knockout on 24-h energy expenditure (kilocalories of heat produced) or physical activity. However, Dyn-/- mice showed increased circulating concentrations of 3,4-dihydroxyphenlacetic acid and 3,4-dihydroxyphenylglycol, suggesting increased activity of the sympathetic nervous system. The respiratory exchange ratio of male but not female Dyn-/- mice was reduced, demonstrating increased fat oxidation. Interestingly, expression of the orexigenic acting NPY in the hypothalamic arcuate nucleus was reduced in Dyn-/- mice. However, fasting-induced increases in pre-prodynorphin expression in the arcuate nucleus, the paraventricular nucleus, and the ventromedial hypothalamus but not the lateral hypothalamus were abolished by deletion of Y1 but not Y2 receptors. Therefore, ablation of dynorphins results in increases in fatty acid oxidation in male mice, reductions in adiposity, and increased weight loss during fasting, possibly via increases in sympathetic activity, decreases in intestinal nutrient absorption, and interactions with the NPYergic system

    Comparability of neuraminidase inhibition antibody titers measured by enzyme-linked lectin assay (ELLA) for the analysis of influenza vaccine immunogenicity

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    AbstractNeuraminidase-inhibition (NI) antibody titers can be used to evaluate the immunogenicity of inactivated influenza vaccines and have provided evidence of serologic cross-reactivity between seasonal and pandemic H1N1 viruses. The traditional thiobarbituric acid assay is impractical for large serologic analyses, and therefore many laboratories use an enzyme-linked lectin assay (ELLA) to determine serum NI antibody titers. The comparability of ELLA NI antibody titers when measured in different laboratories was unknown. Here we report a study conducted through the Consortium for the Standardisation of Influenza SeroEpidemiology (CONSISE) to evaluate the variability of the ELLA. NI antibody titers of a set of 12 samples were measured against both N1 and N2 neuraminidase antigens in 3 independent assays by each of 23 laboratories. For a sample repeated in the same assay, ≄96% of N1 and N2 assays had less than a 4-fold difference in titer. Comparison of the titers measured in assays conducted on 3 different days in the same laboratory showed that a four-fold difference in titer was uncommon. Titers of the same sera measured in different laboratories spanned 3 to 6 two-fold dilutions (i.e., 8–64 fold difference in titer), with an average percent geometric coefficient of variation (%GCV) of 112 and 82% against N1 and N2 antigens, respectively. The difference in titer as indicated by fold range and %GCV was improved by normalizing the NI titers to a standard that was included in each assay. This study identified background signal and the amount of antigen in the assay as critical factors that influence titer, providing important information toward development of a consensus ELLA protocol

    Y2Y4 Receptor Double Knockout Protects Against Obesity Due to a High-Fat Diet or Y1 Receptor Deficiency in Mice

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    Neuropeptide Y receptors are critical regulators of energy homeostasis, but the functional interactions and relative contributions of Y receptors and the environment in this process are unknown. We measured the effects of an ad libitum diet of normal or high-fat food on energy balance in mice with single, double, or triple deficiencies of Y1, Y2, or Y4 receptors. Whereas wild-type mice developed diet-induced obesity, Y2Y4 double knockouts did not. In contrast, Y1 knockout or Y1Y2 or Y1Y4 receptor double knockout mice developed an exacerbated diet-induced obesity syndrome. Remarkably, the antiobesity effect of Y2Y4 deficiency was stronger than the obesogenic effect of Y1 deficiency, since Y1Y2Y4 triple knockouts did not develop obesity on the high-fat diet. Resistance to diet-induced obesity in Y2Y4 knockouts was associated with reduced food intake and improved glucose tolerance in the absence of changes in total physical activity. Fecal concentration of free fatty acids was significantly increased in Y2Y4 knockouts in association with a significantly reduced bile acid pool and marked alterations in intestinal morphology. In addition, hypothalamic proopiomelanocortin expression was decreased in diet-induced obesity (in both wild-type and Y1 receptor knockout mice) but not in obesity-resistant Y2Y4 receptor knockout mice fed a high-fat diet. Therefore, deletion of Y2 and Y4 receptors synergistically protects against diet-induced obesity, at least partially via changes in food intake and hypothalamic proopiomelanocortin expression

    ULF waves in the low‐latitude boundary layer and their relationship to magnetospheric pulsations: A multisatellite observation

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    On April 30 (day 120), 1985, the magnetosphere was compressed at 0923 UT and the subsolar magnetopause remained near 7 REgeocentric for ∌2 hours, during which the four spacecraft Spacecraft Charging At High Altitude (SCATHA), GOES 5, GOES 6, and Active Magnetospheric Particle Tracer Explorers (AMPTE) CCE were all in the magnetosphere on the morning side. SCATHA was in the low-latitude boundary layer (LLBL) in the second half of this period. The interplanetary magnetic field was inferred to be northward from the characteristics of precipitating particle fluxes as observed by the low-altitude satellite Defense Meteorological Satellite Program (DMSP) F7 and also from absence of substorms. We used magnetic field and particle data from this unique interval to study ULF waves in the LLBL and their relationship to magnetic pulsations in the magnetosphere. The LLBL was identified from the properties of particles, including bidirectional field-aligned electron beams at ∌200 eV. In the boundary layer the magnetic field exhibited both a 5–10 min irregular compressional oscillation and a broadband (Δƒ/ƒ ∌ 1) primarily transverse oscillations with a mean period of ∌50 s and a left-hand sense of polarization about the mean field. The former can be observed by other satellites and is likely due to pressure variations in the solar wind, while the latter is likely due to a Kelvin-Helmholtz (K.-H.) instability occurring in the LLBL or on the magnetopause. Also, a strongly transverse ∌3-s oscillation was observed in the LLBL. The magnetospheric pulsations, which exhibited position dependent frequencies, may be explained in terms of field line resonance with a broadband source wave, that is, either the pressure-induced compressional wave or the K.-H. wave generated in or near the boundary layer

    A solution to limitations of cognitive testing in children with intellectual disabilities: the case of fragile X syndrome

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    Intelligence testing in children with intellectual disabilities (ID) has significant limitations. The normative samples of widely used intelligence tests, such as the Wechsler Intelligence Scales, rarely include an adequate number of subjects with ID needed to provide sensitive measurement in the very low ability range, and they are highly subject to floor effects. The IQ measurement problems in these children prevent characterization of strengths and weaknesses, poorer estimates of cognitive abilities in research applications, and in clinical settings, limited utility for assessment, prognosis estimation, and planning intervention. Here, we examined the sensitivity of the Wechsler Intelligence Scale for Children (WISC-III) in a large sample of children with fragile X syndrome (FXS), the most common cause of inherited ID. The WISC-III was administered to 217 children with FXS (age 6–17 years, 83 girls and 134 boys). Using raw norms data obtained with permission from the Psychological Corporation, we calculated normalized scores representing each participant’s actual deviation from the standardization sample using a z-score transformation. To validate this approach, we compared correlations between the new normalized scores versus the usual standard scores with a measure of adaptive behavior (Vineland Adaptive Behavior Scales) and with a genetic measure specific to FXS (FMR1 protein or FMRP). The distribution of WISC-III standard scores showed significant skewing with floor effects in a high proportion of participants, especially males (64.9%–94.0% across subtests). With the z-score normalization, the flooring problems were eliminated and scores were normally distributed. Furthermore, we found correlations between cognitive performance and adaptive behavior, and between cognition and FMRP that were very much improved when using these normalized scores in contrast to the usual standardized scores. The results of this study show that meaningful variation in intellectual ability in children with FXS, and probably other populations of children with neurodevelopmental disorders, is obscured by the usual translation of raw scores into standardized scores. A method of raw score transformation may improve the characterization of cognitive functioning in ID populations, especially for research applications

    An AP-MS- and BioID-compatible MAC-tag enables comprehensive mapping of protein interactions and subcellular localizations

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    Protein-protein interactions govern almost all cellular functions. These complex networks of stable and transient associations can be mapped by affinity purification mass spectrometry (AP-MS) and complementary proximity-based labeling methods such as BioID. To exploit the advantages of both strategies, we here design and optimize an integrated approach combining AP-MS and BioID in a single construct, which we term MAC-tag. We systematically apply the MAC-tag approach to 18 subcellular and 3 sub-organelle localization markers, generating a molecular context database, which can be used to define a protein's molecular location. In addition, we show that combining the AP-MS and BioID results makes it possible to obtain interaction distances within a protein complex. Taken together, our integrated strategy enables the comprehensive mapping of the physical and functional interactions of proteins, defining their molecular context and improving our understanding of the cellular interactome.Peer reviewe
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