212 research outputs found

    Emergent dimensions underlying human understanding of the reachable world

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    Near-scale, reach-relevant environments, like work desks, restaurant place settings or lab benches, are the interface of our hand-based interactions with the world. How are our conceptual representations of these environments organized? For navigable-scale scenes, global properties such as openness, depth or naturalness have been identified, but the analogous organizing principles for reach-scale environments are not known. To uncover such principles, we obtained 1.25 million odd-one-out behavioral judgments on image triplets assembled from 990 reachspace images. Images were selected to comprehensively sample the variation both between and within reachspace categories. Using data-driven modeling, we generated a 30-dimensional embedding which predicts human similarity judgments among the images. First, examination of the embedding dimensions revealed key properties that distinguish among reachspaces, relating to their structural layout, affordances, visual appearances and functional roles. Second, clustering analyses performed over the embedding revealed four distinct interpretable classes of reachspaces, with separate clusters for spaces related to food, electronics, analog activities, and storage or display. Finally, we found that the similarity structure among reachspace images was better predicted by the function of the spaces than their locations, suggesting that reachspaces are largely conceptualized in terms of the actions they are designed to support. Altogether, these results reveal the behaviorally-relevant principles that that structure our internal representations of reach-relevant environments

    Recognizing the need for personalization of haemophilia patient‐reported outcomes in the prophylaxis era

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    Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/134854/1/hae13066.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/134854/2/hae13066_am.pd

    Identification of Disulfide Bond Formation between MitoNEET and Glutamate Dehydrogenase 1

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    MitoNEET is a protein that was identified as a drug target for diabetes, but its cellular function as well as its role in diabetes remains elusive. Protein pull-down experiments identified glutamate dehydrogenase 1 (GDH1) as a potential binding partner. GDH1 is a key metabolic enzyme with emerging roles in insulin regulation. MitoNEET forms a covalent complex with GDH1 through disulfide bond formation and acts as an activator. Proteomic analysis identified the specific cysteine residues that participate in the disulfide bond. This is the first report that effectively links mitoNEET to activation of the insulin regulator GDH1

    Identification of Disulfide Bond Formation between MitoNEET and Glutamate Dehydrogenase 1

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    MitoNEET is a protein that was identified as a drug target for diabetes, but its cellular function as well as its role in diabetes remains elusive. Protein pull-down experiments identified glutamate dehydrogenase 1 (GDH1) as a potential binding partner. GDH1 is a key metabolic enzyme with emerging roles in insulin regulation. MitoNEET forms a covalent complex with GDH1 through disulfide bond formation and acts as an activator. Proteomic analysis identified the specific cysteine residues that participate in the disulfide bond. This is the first report that effectively links mitoNEET to activation of the insulin regulator GDH1

    Similarity in joint function limitation in Type 3 von Willebrand's disease and moderate haemophilia A

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    Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/98234/1/hae12119.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/98234/2/hae12119-sup-0001-AppendixS1.pd

    The history and evolution of the clinical effectiveness of haemophilia type a treatment: a systematic review.

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    First evidence of cases of haemophilia dates from ancient Egypt, but it was when Queen Victoria from England in the 19th century transmitted this illness to her descendants, when it became known as the "royal disease". Last decades of the 20th century account for major discoveries that improved the life expectancy and quality of life of these patients. The history and evolution of haemophilia healthcare counts ups and downs. The introduction of prophylactic schemes during the 1970s have proved to be more effective that the classic on-demand replacement of clotting factors, nevertheless many patients managed with frequent plasma transfusions or derived products became infected with the Human Immunodeficiency Virus (HIV) and Hepatitis C virus during the 1980s and 1990s. Recombinant factor VIII inception has decreased the risk of blood borne infections and restored back longer life expectancies. Main concerns for haemophilia healthcare are shifting from the pure clinical aspects to the economic considerations of long-term replacement therapy. Nowadays researchers' attention has been placed on the future costs and cost-effectiveness of costly long-term treatment. Equity considerations are relevant as well, and alternative options for less affluent countries are under the scope of further research. The aim of this review was to assess the evidence of different treatment options for haemophilia type A over the past four decades, focusing on the most important technological advances that have influenced the natural course of this "royal disease"

    Crystal structure of the mitochondrial protein mitoNEET bound to a benze-sulfonide ligand

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    MitoNEET (gene cisd1) is a mitochondrial outer membrane [2Fe-2S] protein and is a potential drug target in several metabolic diseases. Previous studies have demonstrated that mitoNEET functions as a redox-active and pH-sensing protein that regulates mitochondrial metabolism, although the structural basis of the potential drug binding site(s) remains elusive. Here we report the crystal structure of the soluble domain of human mitoNEET with a sulfonamide ligand, furosemide. Exploration of the high-resolution crystal structure is used to design mitoNEET binding molecules in a pilot study of molecular probes for use in future development of mitochondrial targeted therapies for a wide variety of metabolic diseases, including obesity, diabetes and neurodegenerative diseases such as Alzheimer’s and Parkinson’s disease

    Crystal Structure of the Mitochondrial Protein mitoNEET Bound to a Benze-sulfonide Ligand

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    MitoNEET (gene cisd1) is a mitochondrial outer membrane [2Fe-2S] protein and is a potential drug target in several metabolic diseases. Previous studies have demonstrated that mitoNEET functions as a redox-active and pH-sensing protein that regulates mitochondrial metabolism, although the structural basis of the potential drug binding site(s) remains elusive. Here we report the crystal structure of the soluble domain of human mitoNEET with a sulfonamide ligand, furosemide. Exploration of the high-resolution crystal structure is used to design mitoNEET binding molecules in a pilot study of molecular probes for use in future development of mitochondrial targeted therapies for a wide variety of metabolic diseases, including obesity, diabetes and neurodegenerative diseases such as Alzheimer’s and Parkinson’s disease

    National surveillance for hemophilia inhibitors in the United States: Summary report of an expert meeting: National Inhibitor Surveillance in the U.S.

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    On March 12, 2012, the Centers for Disease Control and Prevention (CDC) held a meeting of its partners in hemophilia treatment, community-based organizations, industry, and government to review data and discuss implementation issues relevant to planned United States (U.S.) national inhibitor surveillance. Issues discussed included the current status of inhibitor surveillance in the United Kingdom (UK) and the US, the results of a US inhibitor surveillance feasibility study, proposed national surveillance schemes, laboratory testing and reporting issues and potential opportunities for future inhibitor-related research. It was concluded that implementation of a national program of inhibitor surveillance using standardized testing through an established public health registry along with patient and care provider education and targeted research provide the best opportunity to inform efforts to develop and evaluate effective prevention strategies

    Socioeconomic, Psychosocial, and Clinical Factors Associated with Employment in Women with HIV in the United States: A Correlational Study

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    Employment is a social determinant of health, and women living with HIV (WLWH) are often underemployed. This correlational study examined the socioeconomic, psychosocial, and clinical factors associated with employment among WLWH (n = 1,357) and women at risk for HIV (n = 560). Descriptive and inferential statistics were used to evaluate factors associated with employment status. Employment was associated (p ≤.05) with better socioeconomic status and quality of life (QOL), less tobacco and substance use, and better physical, psychological, and cognitive health. Among WLWH, employment was associated (p ≤.05) with improved adherence to HIV care visits and HIV RNA viral suppression. Using multivariable regression modeling, differences were found between WLWH and women at risk for HIV. Among WLWH, household income, QOL, education, and time providing childcare remained associated with employment in adjusted multivariable analyses (R2=.272, p <.001). A better understanding of the psychosocial and structural factors affecting employment is needed to reduce occupational disparities among WLWH
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