10 research outputs found

    Knowledge deficit, attitude and behavior scales association to objective measures of sun exposure and sunburn in a Danish population based sample

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    <div><p>The objective of this study was to develop new scales measuring knowledge and attitude about UVR and sun related behavior, and to examine their association to sun related behavior objectively measured by personal dosimetry. During May-August 2013, 664 Danes wore a personal electronic UV-dosimeter for one week that measured their UVR exposure. Afterwards, they answered a questionnaire on sun-related items. We applied descriptive analysis, linear and logistic regression analysis to evaluate the associations between the questionnaire scales and objective UVR measures. Perceiving protection as routine and important were positively correlated with protective behavior. <i>Knowledge deficit of UV and risk of melanoma</i>, <i>perceived benefits</i> and <i>importance of protection behavior</i> was also correlated with use of protection. ‘<i>Knowledge deficit of UV and risk of melanoma</i> and <i>Perceived barrier towards sun avoidance between 12 and 15’</i> were both associated with increased risk of sunburn. <i>Attitude towards tan</i> was associated to both outdoor time and exposure as well as use of protection, but not to sunburn. The results regarding <i>Knowledge deficit of UV and risk of melanoma</i> associated to UVR exposure and <i>Perceived barrier towards sun avoidance between 12 and 15</i> emphasize the importance of awareness of melanoma risk and the priority of the skin cancer prevention advice. Shifting activities to outside the suns peak-hours could be an approach for structural and campaign preventive measures. Knowledge of items predicting exposure to UVR, use of protection and sunburn are important for planning of preventive interventions and melanoma research.</p></div

    Process Development of a Macrocyclic Peptide Inhibitor of PD-L1

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    This article outlines the process development leading to the manufacture of 800 g of BMS-986189, a macrocyclic peptide active pharmaceutical ingredient. Multiple N-methylated unnatural amino acids posed challenges to manufacturing due to the lability of the peptide to cleavage during global side chain deprotection and precipitation steps. These issues were exacerbated upon scale-up, resulting in severe yield loss and necessitating careful impurity identification, understanding the root cause of impurity formation, and process optimization to deliver a scalable synthesis. A systematic study of macrocyclization with its dependence on concentration and pH is presented. In addition, a side chain protected peptide synthesis is discussed where the macrocyclic protected peptide is extremely labile to hydrolysis. A computational study explains the root cause of the increased lability of macrocyclic peptide over linear peptide to hydrolysis. A process solution involving the use of labile protecting groups is discussed. Overall, the article highlights the advancements achieved to enable scalable synthesis of an unusually labile macrocyclic peptide by solid-phase peptide synthesis. The sustainability metric indicates the final preparative chromatography drives a significant fraction of a high process mass intensity (PMI)

    Process Development of a Macrocyclic Peptide Inhibitor of PD-L1

    No full text
    This article outlines the process development leading to the manufacture of 800 g of BMS-986189, a macrocyclic peptide active pharmaceutical ingredient. Multiple N-methylated unnatural amino acids posed challenges to manufacturing due to the lability of the peptide to cleavage during global side chain deprotection and precipitation steps. These issues were exacerbated upon scale-up, resulting in severe yield loss and necessitating careful impurity identification, understanding the root cause of impurity formation, and process optimization to deliver a scalable synthesis. A systematic study of macrocyclization with its dependence on concentration and pH is presented. In addition, a side chain protected peptide synthesis is discussed where the macrocyclic protected peptide is extremely labile to hydrolysis. A computational study explains the root cause of the increased lability of macrocyclic peptide over linear peptide to hydrolysis. A process solution involving the use of labile protecting groups is discussed. Overall, the article highlights the advancements achieved to enable scalable synthesis of an unusually labile macrocyclic peptide by solid-phase peptide synthesis. The sustainability metric indicates the final preparative chromatography drives a significant fraction of a high process mass intensity (PMI)

    Process Development of a Macrocyclic Peptide Inhibitor of PD-L1

    No full text
    This article outlines the process development leading to the manufacture of 800 g of BMS-986189, a macrocyclic peptide active pharmaceutical ingredient. Multiple N-methylated unnatural amino acids posed challenges to manufacturing due to the lability of the peptide to cleavage during global side chain deprotection and precipitation steps. These issues were exacerbated upon scale-up, resulting in severe yield loss and necessitating careful impurity identification, understanding the root cause of impurity formation, and process optimization to deliver a scalable synthesis. A systematic study of macrocyclization with its dependence on concentration and pH is presented. In addition, a side chain protected peptide synthesis is discussed where the macrocyclic protected peptide is extremely labile to hydrolysis. A computational study explains the root cause of the increased lability of macrocyclic peptide over linear peptide to hydrolysis. A process solution involving the use of labile protecting groups is discussed. Overall, the article highlights the advancements achieved to enable scalable synthesis of an unusually labile macrocyclic peptide by solid-phase peptide synthesis. The sustainability metric indicates the final preparative chromatography drives a significant fraction of a high process mass intensity (PMI)

    NATIONAL STATEMENT OF SCIENCE INVESTMENT DRAFT: Response from Rutherford Discovery Fellowship recipients (2010-2013)

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    <p>This is a joint response written and co-signed by 97.5% of New Zealand’s Rutherford Discovery Fellows. We are a group of internationally recognised early- to mid-career researchers who have been selected for our innovative approaches to research across the sciences and the humanities. We work in diverse fields, spanning physical, engineering, information and communications technology, medical, molecular and environmental research through to social sciences, law and the humanities. We are based across a wide cross-section of New Zealand’s Universities and Crown Research Institutes (CRIs), and are engaged in basic, applied and near-to-market research. All of us have directly benefitted from the investments and changes that the Government has been making to the Science sector. As a result of the Rutherford Discovery Fellowship, we have chosen to return to, or to stay in, New Zealand.</p> <p> </p
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