1,694 research outputs found

    Bayesian anomaly detection methods for social networks

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    Learning the network structure of a large graph is computationally demanding, and dynamically monitoring the network over time for any changes in structure threatens to be more challenging still. This paper presents a two-stage method for anomaly detection in dynamic graphs: the first stage uses simple, conjugate Bayesian models for discrete time counting processes to track the pairwise links of all nodes in the graph to assess normality of behavior; the second stage applies standard network inference tools on a greatly reduced subset of potentially anomalous nodes. The utility of the method is demonstrated on simulated and real data sets.Comment: Published in at http://dx.doi.org/10.1214/10-AOAS329 the Annals of Applied Statistics (http://www.imstat.org/aoas/) by the Institute of Mathematical Statistics (http://www.imstat.org

    Social Workers\u27 Perceptions of Family Preservation Programs

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    The passage of the Adoptions and Safe Families Act of 1997, with its focus on child safety and concurrent planning, has presented family preservation workers with new challenges and new opportunities. Twenty volunteers from a large comprehensive social service agency were interviewed to determine their experiences with two models of family preservation—Multisystemic Therapy (MST) and Traditional Family Preservation Service (TFPS) or practice as usual. Workers from both programs were able to articulate values consistent with family preservation as important strengths of the programs— keeping families together and empowering families for example. Information from referring agencies was described as variable and not especially useful when working with seriously troubled families, especially as it related to risk and child safety. Both groups indicated that the jargon of family preservation had permeated their agencies, and that working with other agencies was at times a challenge, though for different reasons. Finally, despite some reservations about the effectiveness of short-term treatment with families that face serious challenges, both groups of workers were generally satisfied with family preservation as an approach to practice

    Cellular localization and trafficking of vascular adhesion protein-1 as revealed by an N-terminal GFP fusion protein

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    Recent studies of vascular adhesion protein-1 (VAP-1) have greatly advanced our understanding of the important role this protein plays in the establishment and progression of inflammatory disease. To facilitate more detailed studies on the function of VAP-1, we developed a GFP-fusion protein that enabled us to monitor the trafficking of the protein in three selected cell types: hepatic sinusoidal endothelial cells, liver myofibroblasts and an hepatic stellate cell line (LX-2). The fusion protein was detected as punctate cytoplasmic GFP staining, but was present only at low levels at the cell surface in all cell types studied. The subcellular distribution of the protein was not altered in a catalytically inactive mutant form of the protein (Tyr471Phe) or in the presence of exogenous VAP-1 substrate (methylamine) or inhibitor (semicarbazide). The GFP-VAP-1 protein was localized to the Golgi apparatus (GM-130), endoplasmic reticulum (GRP94) and early endosomes (EEA-1). Additional staining for VAP-1 revealed that the overexpressed protein was also present in vesicles that were negative for GFP fluorescent signal and did not express EEA-1. We propose that these vesicles are responsible for recycling the fusion protein and that the fluorescence of the GFP moiety is quenched at the low pH within these vesicles. This feature of the protein makes it well suited for live cell imaging studies where we wish to track protein that is being actively trafficked within the cell in preference to that which is being recycled. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00702-013-1003-3) contains supplementary material, which is available to authorized users

    Sport Transitions as Epiphanies

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    Sport managers design development systems with the intent of retaining and advancing athletes through that system (Green, 2005). Important to this basic goal is the participant’s transition from one sport context to another. Transition research has focused primarily on elite athlete’s adaptation to career transitions as they advance at the highest levels or retire from sport (Wylleman & Lavallee, 2004). This orientation places a priority on the external transitions between sport structures before the internal, cognitive development of the athlete. This study examined the transitions of sport participants from an interpretive framework with the goal of understanding the individual’s experience of transition without it necessarily being linked to a typical external change. The sport stories of 48 students at a mid-sized, private university were collected and analyzed utilizing an interpretive paradigm. The disruption stage of these stories represents a time of crisis and transition. Denzin (2001) provided a typology for moments of crisis through four types of epiphanies: major, cumulative, illuminative, and relived. Using this typology of epiphanies can help sport managers to understand these transition events within the life of the participant. Analysis resulted in all disruptions being coded into one of the four original epiphany types. However, a large number of stories were categorized as major epiphanies. Further inductive coding yielded three sub-types of major epiphanies: major bodily, major life change, and major success. The stories within each type or subtype contained similarities in the speed of transition and the breadth of impact of the transition event. For example, stories of major bodily epiphany shared the immediate, life altering impact of significant injury while stories of cumulative shared the slow realization that the sport context had changed without the participant’s realization. Sport managers will be able to use the results of this study to understand and accommodate the pace and breadth of transition experienced by participants in their sport development systems thus maximizing the retention and advancement to the elite ranks

    Autophagy: A cyto-protective mechanism which prevents primary human hepatocyte apoptosis during oxidative stress

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    The role of autophagy in the response of human hepatocytes to oxidative stress remains unknown. Understanding this process may have important implications for the understanding of basic liver epithelial cell biology and the responses of hepatocytes during liver disease. To address this we isolated primary hepatocytes from human liver tissue and exposed them ex vivo to hypoxia and hypoxia-reoxygenation (H-R). We showed that oxidative stress increased hepatocyte autophagy in a reactive oxygen species (ROS) and class III PtdIns3K-dependent manner. Specifically, mitochondrial ROS and NADPH oxidase were found to be key regulators of autophagy. Autophagy involved the upregulation of BECN1, LC3A, Atg7, Atg5 and Atg 12 during hypoxia and H-R. Autophagy was seen to occur within the mitochondria of the hepatocyte and inhibition of autophagy resulted in the lowering a mitochondrial membrane potential and onset of cell death. Autophagic responses were primarily observed in the large peri-venular (PV) hepatocyte subpopulation. Inhibition of autophagy, using 3-methyladenine, increased apoptosis during H-R. Specifically, PV human hepatocytes were more susceptible to apoptosis after inhibition of autophagy. These findings show for the first time that during oxidative stress autophagy serves as a cell survival mechanism for primary human hepatocytes

    Serum-Free Serial Culture of Adult Human Keratinocytes From Suction-Blister Roof Epidermis

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    Coating cell culture flasks with natural extracellular matrix (ECM) enhanced the culture of adult human keratinocytes from suction-blister roof epidermis in an environment without fetal calf serum (FCS), bovine pituitary extracts or cellular feeder layers. A higher incidence of cell attachment on natural ECM was observed than on collagen and human fibronectins(HFN)-coated plastic dishes, and natural ECM was necessary for growth and proliferation of attached cells under the culture conditions used. Cells in primary culture grew to confluency on natural ECM-coated surfaces within about 14 days, and subsequent serial passage could be made up to fourth passage in collagen- and HFN-coated plastic flasks. Cultured keratinocytes in this serum-free environment formed colonies of small cuboidal, healthy cells with little keratinization or stratification and demonstrated antigenic characteristics of human basal cells

    Biochemical and clinical response after umbilical cord blood transplant in a boy with early childhood-onset beta-mannosidosis.

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    BACKGROUND: Deficiency in the enzyme β-mannosidase was described over three decades ago. Although rare in occurrence, the presentation of childhood-onset β-mannosidase deficiency consists of hypotonia in the newborn period followed by global development delay, behavior problems, and intellectual disability. No effective pharmacologic treatments have been available. METHODS: We report 2-year outcomes following the first umbilical cord blood transplant in a 4-year-old boy with early childhood-onset disease. RESULTS: We show restoration of leukocyte β-mannosidase activity which remained normal at 2 years posttransplant, and a simultaneous increase in plasma β-mannosidase activity and dramatic decrease in urine-free oligosaccharides were also observed. MRI of the brain remained stable. Neurocognitive evaluation revealed test point gains, although the magnitude of improvement was less than expected for age, causing lower IQ scores that represent a wider developmental gap between the patient and unaffected peers. CONCLUSION: Our findings suggest that hematopoietic cell transplant can correct the biochemical defect in β-mannosidosis, although preservation of the neurocognitive trajectory may be a challenge

    N-glycan microheterogeneity regulates interactions of plasma proteins

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    Altered glycosylation patterns of plasma proteins are associated with autoimmune disorders and pathogenesis of various cancers. Elucidating glycoprotein microheterogeneity and relating subtle changes in the glycan structural repertoire to changes in protein–protein, or protein–small molecule interactions, remains a significant challenge in glycobiology. Here, we apply mass spectrometry-based approaches to elucidate the global and site-specific microheterogeneity of two plasma proteins: α1-acid glycoprotein (AGP) and haptoglobin (Hp). We then determine the dissociation constants of the anticoagulant warfarin to different AGP glycoforms and reveal how subtle N-glycan differences, namely, increased antennae branching and terminal fucosylation, reduce drug-binding affinity. Conversely, similar analysis of the haptoglobin–hemoglobin (Hp–Hb) complex reveals the contrary effects of fucosylation and N-glycan branching on Hp–Hb interactions. Taken together, our results not only elucidate how glycoprotein microheterogeneity regulates protein–drug/protein interactions but also inform the pharmacokinetics of plasma proteins, many of which are drug targets, and whose glycosylation status changes in various disease states

    Personality States of the Union

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    11 pagesFluctuations in the average daily personality of the United States capture both meaningful affective responses to world events (e.g., changes in anxiety or well-being) and broader psychological responses. We estimate the change in national personality in the months following the onset of the COVID-19 pandemic and investigate fluctuations in personality states during the year 2020 using data from an ongoing personality assessment project. We find significant and meaningful change in personality traits since the beginning of the pandemic, as well as evidence of instability in personality states. When evaluating changes from the first few months of 2020 to the period of social distancing related to COVID-19 restrictions, the social traits reflected an unexpected “deprivation” effect such that mean self-ratings increased in the wake of restricted opportunities for social interaction. Changes in mean levels of the affective traits were not significant over the same months, but they did differ significantly from the average levels of prior years when looking at shorter time intervals (rolling 7-day averages) around prominent national events. This instability may reflect meaningful fluctuations in national personality, as we find that daily personality states are associated with other indices of national health, including daily COVID-19 cases and the S&P index. Overall, the use of personality measures to capture responses to global events offers a more holistic picture of the U.S. psyche and of personality change at the national level
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