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  • 1
    Article
    Article
    Enhanced stability of a protein with increasing temperature (2011)
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    Language: English
    In: Journal of the American Chemical Society, 19 January 2011, Vol.133(2), pp.271-8
    Description: The unusual stability of a structured but locally flexible protein, human growth hormone (hGH) at pH 2.7, was investigated using the temperature dependence of the nanosecond-picosecond dynamics of the backbone amide groups obtained from (15)N NMR relaxation data. It is found that the flexibility of the backbone of the helices decreases with temperature in the range from 24 °C to ∼40 °C, corresponding to an increasing stability. A concomitant increase with temperature of the electrostatic interactions between charged residues forming an interhelical network of salt bridges at the center of the four-helix core suggests that these interactions give rise to the decreasing flexibility and increasing stability of the protein. However, numerous hydrophobic interactions in the interior of the four-helix core may also contribute. Above ∼40 °C, where the thermal energy overcomes the electrostatic and hydrophobic interactions, a substantial increase in the flexibility of the helix backbones results in a highly positive contribution from the local conformational heat capacity, C(p, conf), of the helix backbones to the total heat capacity, C(p), of the protein. This reduces the change in heat capacity upon unfolding, ΔC(p), increases the change in the Gibbs free energy, ΔG(unfold), and stabilizes the protein at high temperatures. A similar decrease in flexibility is found near other salt bridges in hGH and in Calmodulin and may be of general importance for the thermostability of proteins and, in particular, of the salt bridge intensive thermophilic proteins.
    Keywords: Temperature ; Growth Hormone -- Chemistry
    ISSN: 00027863
    E-ISSN: 1520-5126
    DOI: 10.1021/ja105388k
    URL: View this record in MEDLINE/PubMed
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  • 2
    Article
    Article
    Adding and subtracting Black-Scholes: A new approach to approximating derivative prices in continuous-time models (2011)
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    Language: English
    In: Journal of Financial Economics, 2011, Vol.102(2), pp.390-415
    Description: We develop a new approach to approximating asset prices in the context of continuous-time models. For any pricing model that lacks a closed-form solution, we provide a closed-form approximate solution, which relies on the expansion of the intractable model around an “auxiliary” one. We derive an expression for the difference between the true (but unknown) price and the auxiliary one, which we approximate in closed-form, and use to create increasingly improved refinements to the initial mispricing induced by the auxiliary model. The approach is intuitive, simple to implement, and leads to fast and extremely accurate approximations. We illustrate this method in a variety of contexts including option pricing with stochastic volatility, computation of Greeks, and the term structure of interest rates. ► New approach to approximating asset prices in continuous-time models is developed. ► Closed-form approximations are obtained through a series expansion. ► The approach is intuitive, easy to implement, and very precise. ► Numerical examples include option pricing, computation of Greeks, and bond pricing. ► Potential extensions include pricing of exotic contracts and model estimation.
    Keywords: Continuous-Time Models ; Option Pricing Theory ; Stochastic Volatility ; Closed-Form Approximations ; Business ; Economics
    ISSN: 0304-405X
    E-ISSN: 1879-2774
    DOI: 10.1016/j.jfineco.2011.05.007
    URL: View record in ScienceDirect (Access to full text may be restricted)
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  • 3
    Article
    Article
    Strategies to advance vaccine technologies for resource-poor settings (2013)
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    Language: English
    In: Vaccine, April 18, 2013, Vol.31, p.B157-B162
    Description: To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.vaccine.2012.10.113 Byline: Debra Kristensen, Dexiang Chen Keywords: Vaccine; Technology; Formulation; Delivery; Industry; Developing country Abbreviations: AD, autodisable; LIC, low-income country; LMIC, lower-middle-income country; OPV, oral polio vaccine; PDP, product development partnership; R&D, research and development; UNICEF, United Nations Children's Fund; VPPAG, Vaccine Presentation and Packaging Advisory Group; WHO, World Health Organization Abstract: a* Vaccine technologies can improve immunization effectiveness, acceptability, and safety. a* Donor support for vaccine technology development is strong. a* Uptake of proven technologies by the vaccine industry and demand by purchasers continues to lag. a* Article highlights barriers and opportunities from case studies. a* Strategies are proposed to accelerate availability of beneficial vaccine technologies. Author Affiliation: PATH, Seattle, WA 98121, USA
    Keywords: Product Development ; Vaccines ; Public Health
    ISSN: 0264-410X
    Source: Cengage Learning, Inc.
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  • 4
    Article
    Article
    WHO guideline development of paediatric medicines: Points to consider in pharmaceutical development (2012)
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    Language: English
    In: International Journal of Pharmaceutics, 05 October 2012, Vol.435(2), pp.134-135
    Description: To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.ijpharm.2012.05.054 Byline: Henning G. Kristensen Author Affiliation: Faculty of Pharmaceutical Sciences, University of Copenhagen, Universitetsparken 2, DK-2100 Copenhagen O, Denmark
    Keywords: Pharmacy, Therapeutics, & Pharmacology
    ISSN: 0378-5173
    E-ISSN: 1873-3476
    DOI: 10.1016/j.ijpharm.2012.05.054
    URL: View record in ScienceDirect (Access to full text may be restricted)
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  • 5
    Article
    Article
    A diet rich in oat bran improves blood lipids and hemostatic factors, and reduces apparent energy digestibility in young healthy volunteers (2011)
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    In: European Journal of Clinical Nutrition, 2011, Vol.65(9), p.1053
    Description: Background/Objectives: Oat bran shows cholesterol-lowering properties, but its effects on other cardiovascular risk markers are less frequently investigated. This study examined the effects of oat bran on blood lipids, hemostatic factors and energy utilization. Subjects/Methods: A double-blind, randomized crossover study in 24 adults (age 25.2 [+ or -] 2.7 years;body mass index: 24.9 [+ or -] 2.9 kg/[m.sup.2]), who completed two 2-week dietary intervention periods: low-fiber diet (control) or an oat bran (control +102 g oat bran/day) diet. Fasting blood samples were drawn before and after each period, and 3-day fecal samples were collected during the last week of each period. Results: Total cholesterol decreased by 14% during the oat bran period compared with 4% during the control period (P 〈 0.001). Non-high-density lipoprotein (HDL) cholesterol decreased by 16% in the oat bran period compared with 3% in the control period (P 〈 0.01), as did total triacylglycerol (21 vs 10%, P 〈 0.05) and very-low-density lipoprotein triacylglycerol 33 vs 9%, P 〈 0.01). Plasminogen activator inhibitor-1 (PAI-1) and factor VII (fVII) levels decreased more during consumption of oat bran compared with the control period (PAI-1: 30 vs 2.3%, P 〈 0.01; fVII: 15 vs 7.6%, 〈 0.001). Fecal volume and dry matter were greater when consuming the oat bran diet compared with the control (P 〈 0.001), and energy excretion was increased by 37% (1014 vs 638kJ/day, P 〈 0.001); however, changes in body weight did not differ (oat bran:-0.3 [+ or -] 0.5 kg; control: 0.0 [+ or -] 0.7 kg). Conclusions: Addition of oat bran (6 g soluble fiber/day) to a low-fiber diet lowered total and non-HDL cholesterol, as well as hemostatic factors, and may affect energy balance through reduced energy utilization. doi: 10.1038/ejcn.2011.102; published online 8 June 2011 Keywords: oat bran; [beta]-glucan; blood lipids; obesity; apparent digestibility; hemostasis
    Keywords: Diet -- Physiological Aspects ; Diet -- Health Aspects ; Blood Lipids -- Physiological Aspects ; Blood Lipids -- Health Aspects ; Hemostasis -- Research ; Volunteers -- Physiological Aspects ; Volunteers -- Health Aspects ; Energy Metabolism -- Physiological Aspects ; Energy Metabolism -- Health Aspects ; Oat Bran;
    ISSN: 0954-3007
    E-ISSN: 14765640
    DOI: 10.1038/ejcn.2011.102
    URL: View this record in Nature
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  • 6
    Article
    Article
    Colored Petri nets: a graphical language for formal modeling and validation of concurrent systems (2015)
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    Language: English
    In: Communications of the ACM, 21 May 2015, Vol.58(6), pp.61-70
    Description: Formal executable models enable systematic evaluation of system designs prior to implementation and deployment.
    Keywords: Engineering ; Computer Science ; Mathematics
    ISSN: 00010782
    E-ISSN: 1557-7317
    DOI: 10.1145/2663340
    URL: View record in ACM
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  • 7
    Article
    Article
    Arctic herbivore diet can be inferred from stable carbon and nitrogen isotopes in C3 plants, faeces, and wool (2011)
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    In: Canadian Journal of Zoology, September 2011, Vol.89(10), pp.892-899
    Description: The use of stable isotopes in diet analysis usually relies on the different photosynthetic pathways of C3 and C4 plants, and the resulting difference in carbon isotope signature. In the Arctic, however, plant species are exclusively C3, and carbon isotopes alone are therefore not suitable for studying arctic herbivore diets. In this study, we examined the potential of both stable carbon and nitrogen isotopes to reconstruct the diet of an arctic herbivore, here the muskox (Ovibos moschatus (Zimmermann, 1780)), in northeast Greenland. The isotope composition of plant communities and functional plant groups was compared with those of muskox faeces and shed wool, as this is a noninvasive approach to obtain dietary information on different temporal scales. Plants with different root mycorrhizal status were found to have different δ15N values, whereas differences in δ13C, as expected, were less distinct. As a result, our examination mainly relied on stable nitrogen isotopes. The interpretation of stable isotopes from faeces was difficult because of the large uncertainty in diet-faeces fractionation, whereas isotope signatures from wool suggested that the muskox summer diet consists of around 80% graminoids and up to 20% willows. In conclusion, the diet composition of an arctic herbivore can indeed be inferred from stable isotopes in arctic areas, despite the lack of C4 plants.
    Keywords: Diet -- Research ; Wool -- Physiological Aspects ; Wool -- Research ; Photosynthesis -- Research ; Herbivores -- Physiological Aspects ; Herbivores -- Research;
    ISSN: 0008-4301
    E-ISSN: 14803283
    DOI: 10.1139/z11-073
    URL: View source record
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  • 8
    Article
    Article
    Evolutionarily conserved orthologous families in phages are relatively rare in their prokaryotic hosts.(Author abstract)(Report) (2011)
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    Language: English
    In: Journal of Bacteriology, April, 2011, Vol.193(7-8), p.1806(9)
    Description: We have identified conserved orthologs in completely sequenced genomes of double-strand DNA phages and arranged them into evolutionary families (phage orthologous groups [POGs]). Using this resource to analyze the collection of known phage genomes, we find that most orthologs are unique in their genomes (having no diverged duplicates [paralogs]), and while many proteins contain multiple domains, the evolutionary recombination of these domains does not appear to be a major factor in evolution of these orthologous families. The number of POGs has been rapidly increasing over the past decade, the percentage of genes in phage genomes that have orthologs in other phages has also been increasing, and the percentage of unknown "ORFans" is decreasing as more proteins find homoiogs and establish a family. Other properties of phage genomes have remained relatively stable over time, most notably the high fraction of genes that are never or only rarely observed in their cellular hosts. This suggests that despite the renowned ability of phages to transduce cellular genes, these cellular "hitchhiker" genes do not dominate the phage genomic landscape, and a large fraction of the genes in phage genomes maintain an evolutionary trajectory that is distinct from that of the host genes. doi: 10.1128/JB.01311-10
    Keywords: Prokaryotes -- Genetic Aspects ; Prokaryotes -- Physiological Aspects ; Evolution (Biology) -- Research ; Bacteriophages -- Research ; Genomes -- Research ; Host-bacteria Relationships -- Research
    ISSN: 0021-9193
    Source: Cengage Learning, Inc.
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  • 9
    Article
    Article
    Dietary fibres in the regulation of appetite and food intake. Importance of viscosity (2011)
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    Language: English
    In: Appetite, 2011, Vol.56(1), pp.65-70
    Description: Dietary fibres have many functions in the diet, one of which may be to promote control of energy intake and reduce the risk of developing obesity. This is linked to the unique physico-chemical properties of dietary fibres which aid early signalling of satiation and prolonged or enhanced sensation of satiety. Particularly the ability of some dietary fibres to increase viscosity of intestinal contents offers numerous opportunities to affect appetite regulation. Few papers on the satiating effect of dietary fibres include information on the physico-chemical characteristics of the dietary fibres being tested, including molecular weight and viscosity. For viscosity to serve as a proxy for soluble dietary fibres it is essential to have an understanding of individual dietary fibre viscosity characteristics. The goal of this paper is to provide a brief overview on the role of dietary fibres in appetite regulation highlighting the importance of viscosity. ; Includes references ; p. 65-70.
    Keywords: Fiber Content ; Molecular Weight ; Physicochemical Properties ; Dietary Fiber ; Nutrition Physiology ; Appetite ; Humans ; Food Intake ; Literature Reviews ; Fiber Intake
    ISSN: 0195-6663
    URL: View full text (authentication may be required)
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  • 10
    Article
    Article
    Vaccine stabilization: Research, commercialization, and potential impact (2011)
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    Language: English
    In: Vaccine, 22 September 2011, Vol.29(41), pp.7122-7124
    Description: All vaccines are susceptible to damage by elevated temperatures and many are also damaged by freezing. The distribution, storage, and use of vaccines therefore present challenges that could be reduced by enhanced thermostability, with resulting improvements in vaccine effectiveness. Formulation and processing technologies exist that can improve the stability of vaccines at temperature extremes, however, customization is required for individual vaccines and results are variable. Considerations affecting decisions about stabilization approaches include development cost, manufacturing cost, and the ease of use of the final product. Public sector agencies can incentivize vaccine developers to prioritize stabilization efforts through advocacy and by implementing policies that increase demand for thermostable vaccines.
    Keywords: Vaccine ; Stability ; Policy ; Medicine ; Biology ; Veterinary Medicine ; Pharmacy, Therapeutics, & Pharmacology
    ISSN: 0264-410X
    E-ISSN: 1873-2518
    DOI: 10.1016/j.vaccine.2011.05.070
    URL: View record in ScienceDirect (Access to full text may be restricted)
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