1,099 research outputs found

    Legal Issues in Child Welfare Cases Involving Children with Disabilities

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    This chapter examines the legal framework applicable when child maltreatment and disability intersect. It begins with a brief description of the constitutional foundation forparent-child-state relations. It provides an overview of relevant federal child welfare laws, which today shape each state’s child protection system. It then considers the application of various federal laws governing work with children and families when a child has a disability. In doing so, we consider the Americans with Disabilities Act, the Individuals with Disabilities Education Act, and Section 504 of the Rehabilitation Act, and we touch upon Social Security benefits for children. This chapter does not examine child well-being legislation that establishes and funds programs such as Temporary Assistance to Needy Families (TANF), Supplemental Nutrition Assistance Program (SNAP), or publicly funded health care for children such as the State Children’s Health Insurance Program

    A Review of Layer Based Manufacturing Processes for Metals

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    The metal layered manufacturing processes have provided industries with a fast method to build functional parts directly from CAD models. This paper compares current metal layered manufacturing technologies from including powder based metal deposition, selective laser sinstering (SLS), wire feed deposition etc. The characteristics of each process, including its industrial applications, advantages/disadvantages, costs etc are discussed. In addition, the comparison between each process in terms of build rate, suitable metal etc. is presented in this paper.Mechanical Engineerin

    Mass spectrometric characterisation of the circulating peptidome following oral glucose ingestion in control and gastrectomised patients.

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    RATIONALE: Meal ingestion triggers secretion of a variety of gut and endocrine peptides important in diabetes research which are routinely measured by immunoassays. However, similarities between some peptides (glucagon, oxyntomodulin and glicentin) can cause specificity issues with immunoassays. We used a liquid chromatography/tandem mass spectrometry (LC/MS/MS) methodology to unambiguously monitor multiple gut peptides in human plasma. METHODS: A simple acetonitrile-based protein precipitation step, followed by evaporation and solid-phase extraction, removed high-abundance proteins from samples prior to nano-LC/MS/MS analysis on an Orbitrap Q-Exactive Plus mass spectrometer using a data-dependent methodology. Database searching using PEAKS identified multiple gut-derived peptides, including peptides in the mid-pg/mL range. The relative levels of these and previously characterised peptides were assessed in plasma samples from gastrectomised and control subjects during an oral glucose tolerance test. RESULTS: Analysis of plasma extracts revealed significantly elevated levels of a number of peptides following glucose ingestion in subjects who had undergone gastrectomy compared with controls. These included GLP-1(7-36), GLP-1(9-36), glicentin, oxyntomodulin, GIP(1-42), GIP(3-42), PYY(1-36), PYY(3-36), neurotensin, insulin and C-peptide. Motilin levels decreased following glucose ingestion. Results showed good correlation with immunoassay-derived concentrations of some peptides in the same samples. The gastrectomy group also had higher, but non-glucose-dependent, circulating levels of peptides from PIGR and DMBT1. CONCLUSIONS: Overall, the approach showed that a fast, generic and reproducible LC/MS/MS methodology requiring only a small volume of plasma was capable of the multiplexed detection of a variety of diabetes-related peptides.Wellcome Trust and MR

    Spectators’ aesthetic experience of sound and movement in dance performance:a transdisciplinary investigation

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    We utilize qualitative audience research and functional brain imaging (fMRI) to examine the aesthetic experience of watching dance both with and without music. This transdisciplinary approach was motivated by the recognition that the aesthetic experience of dance revealed through conscious interpretation could have neural correlates in brain activity. When audiences were engaged in watching dance accompanied by music, the fMRI data revealed evidence of greater intersubject correlation in a left anterior region of the superior temporal gyrus known to be involved in complex audio processing. Moreover, the qualitative data revealed how spectators derived pleasure from finding convergences between 2 complex stimuli (dance and music). Without music, greater intersubject correlation was found bilaterally in a posterior region of the superior temporal gyrus, showing that bodily sounds such as breath provide a more salient auditory signal than music in primary auditory regions. Watching dance without music also resulted in increased intersubject correlation among spectators in the parietal and occipitotemporal cortices, suggesting a greater influence of the body than when interpreting the dance stimuli with music. Similarly, the audience research found evidence of corporeally focused experience, but suggests that while embodied responses were common across spectators, they were accompanied by different evaluative judgments

    Human IgG antibody profiles differentiate between symptomatic patients with and without colorectal cancer

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    Abstract OBJECTIVE: Patients with cancer have antibodies against tumour antigens. Characterising the antibody repertoire may provide insights into aberrant cellular mechanisms in cancer development, ultimately leading to novel diagnostic or therapeutic targets. The aim of this study was to characterise the antibody profiles in patients whose symptoms warranted colonoscopy, to see if there was a difference in patients with and without colorectal cancer. METHODS: Patients were recruited from a colonoscopy clinic. Individual serum samples from 43 patients with colorectal cancer and 40 patients with no cancer on colonoscopy were profiled on a 37 830 clone recombinant human protein array. Antigen expression was evaluated by quantitative reverse transcription-PCR and by immunohistochemistry on tissue microarrays. RESULTS: Using a sex- and age-matched training set, 18 antigens associated with cancer and 4 associated with the absence of cancer (p\u3c0.05) were identified and confirmed. To investigate the mechanisms triggering antibody responses to these antigens, antigen expression was examined in normal colorectal mucosa and colorectal carcinoma of the same patients. The identified antigens showed cellular accumulation (p53), aberrant cellular expression (high mobility group B1 (HMGB1)) and overexpression (tripartite motif-containing 28 (TRIM28), p53, HMGB1, transcription factor 3 (TCF3), longevity assurance gene homologue 5 (LASS5) and zinc finger protein 346 (ZNF346)) in colorectal cancer tissue compared with normal colorectal mucosa. CONCLUSIONS: It is demonstrated for the first time that screening high-density protein arrays identifies unique antibody profiles that discriminate between symptomatic patients with and without colorectal cancer. The differential expression of identified antigens suggests their involvement in aberrant cellular mechanisms in cance

    BOWiki: an ontology-based wiki for annotation of data and integration of knowledge in biology.

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    MOTIVATION: Ontology development and the annotation of biological data using ontologies are time-consuming exercises that currently require input from expert curators. Open, collaborative platforms for biological data annotation enable the wider scientific community to become involved in developing and maintaining such resources. However, this openness raises concerns regarding the quality and correctness of the information added to these knowledge bases. The combination of a collaborative web-based platform with logic-based approaches and Semantic Web technology can be used to address some of these challenges and concerns. RESULTS: We have developed the BOWiki, a web-based system that includes a biological core ontology. The core ontology provides background knowledge about biological types and relations. Against this background, an automated reasoner assesses the consistency of new information added to the knowledge base. The system provides a platform for research communities to integrate information and annotate data collaboratively. AVAILABILITY: The BOWiki and supplementary material is available at . The source code is available under the GNU GPL from

    Characterization of resistance to a potent D-peptide HIV entry inhibitor.

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    BACKGROUND: PIE12-trimer is a highly potent D-peptide HIV-1 entry inhibitor that broadly targets group M isolates. It specifically binds the three identical conserved hydrophobic pockets at the base of the gp41 N-trimer with sub-femtomolar affinity. This extremely high affinity for the transiently exposed gp41 trimer provides a reserve of binding energy (resistance capacitor) to prevent the viral resistance pathway of stepwise accumulation of modest affinity-disrupting mutations. Such modest mutations would not affect PIE12-trimer potency and therefore not confer a selective advantage. Viral passaging in the presence of escalating PIE12-trimer concentrations ultimately selected for PIE12-trimer resistant populations, but required an extremely extended timeframe (\u3e 1 year) in comparison to other entry inhibitors. Eventually, HIV developed resistance to PIE12-trimer by mutating Q577 in the gp41 pocket. RESULTS: Using deep sequence analysis, we identified three mutations at Q577 (R, N and K) in our two PIE12-trimer resistant pools. Each point mutant is capable of conferring the majority of PIE12-trimer resistance seen in the polyclonal pools. Surface plasmon resonance studies demonstrated substantial affinity loss between PIE12-trimer and the Q577R-mutated gp41 pocket. A high-resolution X-ray crystal structure of PIE12 bound to the Q577R pocket revealed the loss of two hydrogen bonds, the repositioning of neighboring residues, and a small decrease in buried surface area. The Q577 mutations in an NL4-3 backbone decreased viral growth rates. Fitness was ultimately rescued in resistant viral pools by a suite of compensatory mutations in gp120 and gp41, of which we identified seven candidates from our sequencing data. CONCLUSIONS: These data show that PIE12-trimer exhibits a high barrier to resistance, as extended passaging was required to develop resistant virus with normal growth rates. The primary resistance mutation, Q577R/N/K, found in the conserved gp41 pocket, substantially decreases inhibitor affinity but also damages viral fitness, and candidate compensatory mutations in gp160 have been identified
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