2,151 research outputs found

    The Role Body-Esteem Plays in Impairment Associated with Hair-Pulling and Skin Picking in Adolescents

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    Trichotillomania (hair pulling disorder, HPD) and pathological skin picking (PSP) are associated with significant rates of psychosocial impairment and distress. Little research has addressed the physical consequences and associated impairment in youth (e.g., poor body-esteem). The present study explores the relationship between body-esteem, skin picking (SP), and pulling-related impairment in a sample of adolescents with primary HPD. Ninety four adolescents who pull their hair, 40 of whom also pick their skin, were recruited via internet-sampling as part of the Child and Adolescent Trichotillomania Impact Study (CA-TIP). All youth and a parent completed anonymous questionnaires online assessing psychiatric symptoms, repetitive behaviors, and psychosocial impairment, among other variables. Appearance-based body-esteem was not found to be predictive of more severe psychosocial impairment in these youth. However, SP, in combination with HPD, contributed to worse appearance-based body-esteem above and beyond symptoms of HPD alone. The current study suggests that psychosocial functioning in youth with HPD is less impacted by body-esteem or pulling than other factors (e.g., depression and anxiety), and that SP contributes to lowered body-esteem. These findings suggest the importance of addressing body-esteem in case conceptualization for youth with both HPD and SP. Further research is required to confirm these suggestions

    Understanding Therapeutic Monoclonal Antibody Aggregation Mechanisms through Biophysical, Biochemical and Biological Characterization of Two Types of Immunoglobulin G Dimers

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    Aggregation has been identified as one of the major degradation pathways that affect the quality and efficacy of protein therapeutics. Dimers are one of the predominant oligomeric species found in monoclonal antibody (mAb) based products, whose formation can occur both during processing and long-term storage, and following exposure to certain accelerated stress conditions. It has been hypothesized that these dimeric species could be the initial step on the mAb protein aggregation pathway, but this has been difficult to establish since mAb dimers can be a heterogeneous population of molecules. In this study, two mAb dimer species were generated and isolated from IgG2 monoclonal antibody samples, one upon long-term storage and the other from elevated stress conditions. The dimer-enriched fractions were characterized for protein conformation, morphology, structural integrity and bioactivity. The results revealed both common properties and unique differences between the two types of mAb dimers generated under these two different conditions. The findings of this study provide insights towards greater understanding of the possible causes of dimer formation under native storage and thermal stress conditions for this IgG2 mAb, and two possible mechanisms of dimer formation are proposed

    The Body Ontology of Capitalism

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    Critical social theory powerfully negates symbolic structures of political economy and imaginary projections of ideological culture but never quite knows what to do with corporeal bodies. “The Body Ontology of Capitalism” reviews Marx’s account of body ontology in his post-1859 writings (especially Capital, Vol. 1), in which value (abstract labor) is extracted from the concrete bodies of laborers caught in capital’s grasp. Body ontology is analyzed in Marx’s work as well as Lacan’s psychoanalytic social theory, exploring the relationship between structurally wounded bodies and imaginary projections. Zižek’s embodied account of wounded subjects of sublime ideological objects is also used to interpret the body fantasies of late capitalism (undead, cyborg, armored subjects). Following Marx and psychoanalytic theorists, Krier and Amidon conclude that body ontology is necessary to adequately comprehend and critique symbolic and imaginary productions of capital

    Exploration of the structural requirements of Aurora Kinase B inhibitors by a combined QSAR, modelling and molecular simulation approach

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    Aurora kinase B plays an important role in the cell cycle to orchestrate the mitotic process. The amplification and overexpression of this kinase have been implicated in several human malignancies. Therefore, Aurora kinase B is a potential drug target for anticancer therapies. Here, we combine atom-based 3D-QSAR analysis and pharmacophore model generation to identify the principal structural features of acylureidoindolin derivatives that could potentially be responsible for the inhibition of Aurora kinase B. The selected CoMFA and CoMSIA model showed significant results with cross-validation values (q(2)) of 0.68, 0.641 and linear regression values (r(2)) of 0.971, 0.933 respectively. These values support the statistical reliability of our model. A pharmacophore model was also generated, incorporating features of reported crystal complex structures of Aurora kinase B. The pharmacophore model was used to screen commercial databases to retrieve potential lead candidates. The resulting hits were analyzed at each stage for diversity based on the pharmacophore model, followed by molecular docking and filtering based on their interaction with active site residues and 3D-QSAR predictions. Subsequently, MD simulations and binding free energy calculations were performed to test the predictions and to characterize interactions at the molecular level. The results suggested that the identified compounds retained the interactions with binding residues. Binding energy decomposition identified residues Glu155, Trp156 and Ala157 of site B and Leu83 and Leu207 of site C as major contributors to binding affinity, complementary to 3D-QSAR results. To best of our knowledge, this is the first comparison of WaterSwap field and 3D-QSAR maps. Overall, this integrated strategy provides a basis for the development of new and potential AK-B inhibitors and is applicable to other protein targets

    Functional Properties of Human Auditory Cortical Fields

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    While auditory cortex in non-human primates has been subdivided into multiple functionally specialized auditory cortical fields (ACFs), the boundaries and functional specialization of human ACFs have not been defined. In the current study, we evaluated whether a widely accepted primate model of auditory cortex could explain regional tuning properties of fMRI activations on the cortical surface to attended and non-attended tones of different frequency, location, and intensity. The limits of auditory cortex were defined by voxels that showed significant activations to non-attended sounds. Three centrally located fields with mirror-symmetric tonotopic organization were identified and assigned to the three core fields of the primate model while surrounding activations were assigned to belt fields following procedures similar to those used in macaque fMRI studies. The functional properties of core, medial belt, and lateral belt field groups were then analyzed. Field groups were distinguished by tonotopic organization, frequency selectivity, intensity sensitivity, contralaterality, binaural enhancement, attentional modulation, and hemispheric asymmetry. In general, core fields showed greater sensitivity to sound properties than did belt fields, while belt fields showed greater attentional modulation than core fields. Significant distinctions in intensity sensitivity and contralaterality were seen between adjacent core fields A1 and R, while multiple differences in tuning properties were evident at boundaries between adjacent core and belt fields. The reliable differences in functional properties between fields and field groups suggest that the basic primate pattern of auditory cortex organization is preserved in humans. A comparison of the sizes of functionally defined ACFs in humans and macaques reveals a significant relative expansion in human lateral belt fields implicated in the processing of speech

    Experiences in deploying metadata analysis tools for institutional repositories

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    Current institutional repository software provides few tools to help metadata librarians understand and analyze their collections. In this article, we compare and contrast metadata analysis tools that were developed simultaneously, but independently, at two New Zealand institutions during a period of national investment in research repositories: the Metadata Analysis Tool (MAT) at The University of Waikato, and the Kiwi Research Information Service (KRIS) at the National Library of New Zealand. The tools have many similarities: they are convenient, online, on-demand services that harvest metadata using OAI-PMH; they were developed in response to feedback from repository administrators; and they both help pinpoint specific metadata errors as well as generating summary statistics. They also have significant differences: one is a dedicated tool wheres the other is part of a wider access tool; one gives a holistic view of the metadata whereas the other looks for specific problems; one seeks patterns in the data values whereas the other checks that those values conform to metadata standards. Both tools work in a complementary manner to existing Web-based administration tools. We have observed that discovery and correction of metadata errors can be quickly achieved by switching Web browser views from the analysis tool to the repository interface, and back. We summarize the findings from both tools' deployment into a checklist of requirements for metadata analysis tools

    Entanglement model of antibody viscosity

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    Antibody solutions are typically much more viscous than solutions of globular proteins at equivalent volume fraction. Here we propose that this is due to molecular entanglements that are caused by the elongated shape and intrinsic flexibility of antibody molecules. We present a simple theory in which the antibodies are modeled as linear polymers that can grow via reversible bonds between the antigen binding domains. This mechanism explains the observation that relatively subtle changes to the interparticle interaction can lead to large changes in the viscosity. The theory explains the presence of distinct power law regimes in the concentration dependence of the viscosity as well as the correlation between the viscosity and the charge on the variable domain in our anti-streptavidin IgG1 model system

    An undernutrition screening score for dogs with protein‐losing enteropathy: A prospective multicenter study

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    BACKGROUND: The impact of undernutrition in dogs with protein-losing enteropathy (PLE) caused by inflammatory enteritis, intestinal lymphangiectasia, or both and which variables are most predictive of outcome are unknown. OBJECTIVES: Develop an undernutrition screening score (USS) for use at the time of diagnosis of PLE in dogs, which is predictive of outcome. ANIMALS: Fifty-seven dogs with PLE prospectively recruited from 3 referral hospitals in the United Kingdom. METHODS: An USS based on the presence and severity of 5 variables: appetite, weight loss, and body, muscle, and coat condition and scored out of 15, with higher scores reflecting worse undernutrition, was calculated at the time of diagnosis. Follow-up information was obtained for at least 6 months. RESULTS: Dogs that failed to achieve clinical remission within 6 months had higher USS at diagnosis compared with dogs that achieved remission (median, 7.5; range, 2-14 and median, 5; range, 0-14, respectively). The USS at diagnosis gave an area under the receiver operating characteristic curve (AUC) of 0.656 for predicting nonclinical remission within 6 months, whereas a score consisting of just epaxial muscle loss and coat condition resulted in a larger AUC of 0.728. CONCLUSIONS AND CLINICAL IMPORTANCE: Of the 5 variables assessed in the USS, a combination of epaxial muscle loss and coat condition was most predictive of not achieving clinical remission within 6 months in dogs with PLE. Additional studies will help determine the effect of changes in USS and the 5 associated variables after diagnosis on outcome variables in these dogs

    Statistical properties of SGR 1900+14 bursts

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    We study the statistics of soft gamma repeater (SGR) bursts, using a data base of 187 events detected with BATSE and 837 events detected with RXTE PCA, all from SGR 1900+14 during its 1998-1999 active phase. We find that the fluence or energy distribution of bursts is consistent with a power law of index 1.66, over 4 orders of magnitude. This scale-free distribution resembles the Gutenberg-Richter Law for earthquakes, and gives evidence for self-organized criticality in SGRs. The distribution of time intervals between successive bursts from SGR 1900+14 is consistent with a log-normal distribution. There is no correlation between burst intensity and the waiting times till the next burst, but there is some evidence for a correlation between burst intensity and the time elapsed since the previous burst. We also find a correlation between the duration and the energy of the bursts, but with significant scatter. In all these statistical properties, SGR bursts resemble earthquakes and solar flares more closely than they resemble any known accretion-powered or nuclear-powered phenomena. Thus our analysis lends support to the hypothesis that the energy source for SGR bursts is internal to the neutron star, and plausibly magnetic.Comment: 11 pages, 4 figures, accepted for publication in ApJ
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