943 research outputs found

    Encapsulation of tetrahedral anions in nickel mesocate cages : a thesis presented in partial fulfilment of the requirements for the degree of Master of Science in Chemistry at Massey University, Manawatu, New Zealand

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    Finding ways to isolate anions and metals is a modern problem as concerns over pollution of anions have become popular in the scientific community. The applications of supramolecular structures are endless, ranging from drug delivery to refining metals at an industrial scale. In this thesis, three variations of a di-salicylaldimine linked ligands were designed to form anion encapsulating mesocates. Each ligand differs by the spacer linking the salicylaldimine units. L1 has a six-carbon spacer, L2 has a p-xylylic spacer and L3 has a m-xylylic spacer. After the synthesis and characterisation of these ligands, complexation was achieved with various nickel salts resulting in the formation of dinuclear triple-stranded mesocate complexes; [BF₄⊂Ni₂(L1)₃](BF₄)₃ (C1), [ClO₄⊂Ni₂(L1)₃](ClO₄)₃ (C2) and two dinuclear di-stranded mesocate complexes; [SO₄⊂Ni₂(L3)₂][Ni(SO₄)₂ (EtOH)₄] (C3), [ClO₄⊂Ni₂(L3)₂](ClO₄)₂ (C4). The crystals have been characterised with IR spectroscopy, UV-Vis spectroscopy, mass spectrometry, atomic absorption spectroscopy, conductivity measurements and single crystal X-ray diffraction. An uncommon mesocate structure was observed from the X-ray diffraction data collected whereby the anion in the centre of the cage forms covalent bonds with the two Ni²⁺ metal ions. In addition, metal salt extraction experiments were attempted in a two-phase solvent system with L3, nickel sulfate to assess how much nickel and sulfate could be extracted from the aqueous mixture to the organic solution. Although a reliable measurement of sulfate could not be obtained, the highest percentage of the nickel extracted measured in hexane was 89%. However, there is potential to gather a higher value using the optimal conditions found in these experiments

    Novel personalized pathway-based metabolomics models reveal key metabolic pathways for breast cancer diagnosis

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    Comparison of logistic regression, SVM and random forest performance in the plasma training data set. Table S2. Pathway significance and relative log fold changes in our metabolomics data and TCGA breast cancer RNA-Seq data. Table S3. Detected metabolites and their differential test results among the two models. a All-stage diagnosis model. b Early-stage diagnosis model. Table S4. Single-variate logistic analysis of metabolites or pathways selected as features in the metabolite-based or pathway-based early-stage diagnosis model. Table S5. Comparison of pathway features in the full-size (101 input pathways) and half-size (51 input pathways) pathway-based early-stage diagnosis models. (DOCX 34 kb

    A Social Media Policy for Clinical Mental Health Counseling Programs

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    The American Counseling Association 2014 Ethical Code mandates that counselors who engage in social media communication develop knowledge and skills related to ethical and legal considerations (American Counseling Association, 2014). In response to these expectations, this article introduces a social media policy created by faculty in a Clinical Mental Health Counseling program. An example and review of an implemented social media policy is provided, along with guidelines for a student-led training program. Case examples are provided that illustrate potential dilemmas of student misuse of social media, along with examples of faculty interventions. This article is designed to contribute to the professional discourse on how to address social media and technology in counselor training

    Married adolescents: An overview

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    The nascent work reviewed in this compendium indicates that married girls experience significant social isolation and limited autonomy. Across the studies examined, on indicators of mobility, exposure to media, and social networks, married girls are consistently disadvantaged compared to their unmarried peers. Similarly, across studies, on most of the domains explored here (mobility, decision-making, control over economic resources, and possibly gender-based violence), married girls tend to be less empowered and more isolated than slightly older married females. There may also be health issues associated with marriage during adolescence. Married girls are frequently at a disadvantage in terms of reproductive health information—particularly regarding STIs and HIV. First-time mothers, many of whom are adolescents, by virtue of their parity may have distinct maternal health needs and risks. Finally, early marriage potentially plays a role in exposing girls and young women to severe reproductive health risks, including HIV. Many of these elevated health risks may be largely, though not exclusively, derivative of their social vulnerability

    A world apart: The disadvantage and social isolation of married adolescent girls

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    This brief is based on a paper prepared for the WHO/UNFPA/Population Council Technical Consultation on Married Adolescents, held in Geneva, Switzerland, December 9–12, 2003. The consultation brought together experts from the United Nations, donors, and nongovernmental agencies to consider the evidence regarding married adolescent girls’ reproductive health, vulnerability to HIV infection, social and economic disadvantage, and rights. The relationships to major policy initiatives—including safe motherhood, HIV, adolescent sexual and reproductive health, and reproductive rights—were explored, and emerging findings from the still relatively rare programs that are directed at this population were discussed. Despite the program attention and funding that have been devoted to adolescents, early marriage and married adolescents have fallen largely outside of the field’s concern. Comprising the majority of sexually active adolescent girls in developing countries, this large and vulnerable subpopulation has received neither program and policy consideration in the adolescent sexual and reproductive health field, nor special attention from reproductive health and development programs for adult women. While adolescent girls, irrespective of marital status, are vulnerable in many settings and deserve program, policy, and resource support, the purpose of this brief is to describe the distinctive and often disadvantaged situations of married girls and to propose possible future policy and program options

    A novel secreted protein, MYR1, is central to Toxoplasma’s manipulation of host cells

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    The intracellular protozoan Toxoplasma gondii dramatically reprograms the transcriptome of host cells it infects, including substantially up-regulating the host oncogene c-myc. By applying a flow cytometry-based selection to infected mouse cells expressing green fluorescent protein fused to c-Myc (c-Myc–GFP), we isolated mutant tachyzoites defective in this host c-Myc up-regulation. Whole-genome sequencing of three such mutants led to the identification of MYR1 (Myc regulation 1; TGGT1_254470) as essential for c-Myc induction. MYR1 is a secreted protein that requires TgASP5 to be cleaved into two stable portions, both of which are ultimately found within the parasitophorous vacuole and at the parasitophorous vacuole membrane. Deletion of MYR1 revealed that in addition to its requirement for c-Myc up-regulation, the MYR1 protein is needed for the ability of Toxoplasma tachyzoites to modulate several other important host pathways, including those mediated by the dense granule effectors GRA16 and GRA24. This result, combined with its location at the parasitophorous vacuole membrane, suggested that MYR1 might be a component of the machinery that translocates Toxoplasma effectors from the parasitophorous vacuole into the host cytosol. Support for this possibility was obtained by showing that transit of GRA24 to the host nucleus is indeed MYR1-dependent. As predicted by this pleiotropic phenotype, parasites deficient in MYR1 were found to be severely attenuated in a mouse model of infection. We conclude, therefore, that MYR1 is a novel protein that plays a critical role in how Toxoplasma delivers effector proteins to the infected host cell and that this is crucial to virulence

    Integrating NGS-derived mutational profiling in the diagnosis of multiple lung adenocarcinomas

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    MICROABSTRACT: Integration of Next Generation Sequencing (NGS) information for use in distinguishing between Multiple Primary Lung Cancer and intrapulmonary metastasis was evaluated. We used a probabilistic model, comprehensive histologic assessment and NGS to classify patients. Integrating NGS data confirmed initial diagnosis (n = 41), revised the diagnosis (n = 12), while resulted in non-informative data (n = 8). Accuracy of diagnosis can be significantly improved with integration of NGS data. BACKGROUND: Distinguishing between multiple primary lung cancers (MPLC) and intrapulmonary metastases (IPM) is challenging. The goal of this study was to evaluate how Next Generation Sequencing (NGS) information may be integrated in the diagnostic strategy. PATIENTS AND METHODS: Patients with multiple lung adenocarcinomas were classified using both the comprehensive histologic assessment and NGS. We computed the joint probability of each pair having independent mutations by chance (thus being classified as MPLC). These probabilities were computed using the marginal mutation rates of each mutation, and the known negative dependencies between driver genes and different gene loci. With these NGS-driven data, cases were re-classified as MPLC or IPM. RESULTS: We analyzed 61 patients with a total of 131 tumors. The most frequent mutation was KRAS (57.3%) which occured at a rate higher than expected (p < 0.001) in lung cancer. No mutation was detected in 25/131 tumors (19.1%). Discordant molecular findings between tumor sites were found in 46 patients (75.4%); 11 patients (18.0%) had concordant molecular findings, and 4 patients (6.6%) had concordant molecular findings at 2 of the 3 sites. After integration of the NGS data, the initial diagnosis was confirmed for 41 patients (67.2%), the diagnosis was revised for 12 patients (19.7%) or was considered as non-informative for 8 patients (13.1%). CONCLUSION: Integrating the information of NGS data may significantly improve accuracy of diagnosis and staging

    Correlating Gastrointestinal Histopathologic Changes to Clinical Disease Activity in Dogs With Idiopathic Inflammatory Bowel Disease

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    Prior studies have failed to detect a convincing association between histologic lesions of inflammation and clinical activity in dogs with inflammatory bowel disease (IBD). We hypothesized that use of a simplified histopathologic scoring system would improve the consistency of interpretation among pathologists when describing histologic lesions of gastrointestinal inflammation. Our aim was to evaluate the correlation of histopathologic changes to clinical activity in dogs with IBD using this new system. Forty-two dogs with IBD and 19 healthy control dogs were enrolled in this retrospective study. Endoscopic biopsies from the stomach, duodenum, ileum, and colon were independently scored by 8 pathologists. Clinical disease activity was scored using the Canine Inflammatory Bowel Disease Activity Index (CIBDAI) or the Canine Chronic Enteropathy Clinical Activity Index (CCECAI), depending on the individual study center. Summative histopathological scores and clinical activity were calculated for each tissue (stomach, duodenum, ileum, and colon) and each tissue histologic score (inflammatory/morphologic feature). The correlation between CCECAI/CIBDAI and summative histopathologic score was significant (P < .05) for duodenum (r = 0.42) and colon (r = 0.33). In evaluating the relationship between histopathologic scores and clinical activity, significant (P < .05) correlations were observed for crypt dilation (r = 0.42), lamina propria (LP) lymphocytes (r = 0.40), LP neutrophils (r = 0.45), mucosal fibrosis (r = 0.47), lacteal dilation (r = 0.39), and villus stunting (r = 0.43). Compared to earlier grading schemes, the simplified scoring system shows improved utility in correlating histopathologic features (both summative histology scores and select histologic scores) to IBD clinical activity

    A common NFKB1 variant detected through antibody analysis in UK Biobank predicts risk of infection and allergy

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    Infectious agents contribute significantly to the global burden of diseases through both acute infection and their chronic sequelae. We leveraged the UK Biobank to identify genetic loci that influence humoral immune response to multiple infections. From 45 genome-wide association studies in 9,611 participants from UK Biobank, we identified NFKB1 as a locus associated with quantitative antibody responses to multiple pathogens, including those from the herpes, retro-, and polyoma-virus families. An insertion-deletion variant thought to affect NFKB1 expression (rs28362491), was mapped as the likely causal variant and could play a key role in regulation of the immune response. Using 121 infection- and inflammation-related traits in 487,297 UK Biobank participants, we show that the deletion allele was associated with an increased risk of infection from diverse pathogens but had a protective effect against allergic disease. We propose that altered expression of NFKB1, as a result of the deletion, modulates hematopoietic pathways and likely impacts cell survival, antibody production, and inflammation. Taken together, we show that disruptions to the tightly regulated immune processes may tip the balance between exacerbated immune responses and allergy, or increased risk of infection and impaired resolution of inflammation
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