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Thermal Stabilization of Oxytocin and Fibroblast Growth Factor 2 (FGF2)
Get PDFOxytocin is a uterotonic neuropeptide. It has been recommended by the World Health Organization (WHO) as the first line treatment to prevent and treat postpartum hemorrhage (PPH). PPH is the main cause of maternal deaths (27.1%) in many low-income countries. Basic fibroblast growth factor (FGF2) is one of the family members of fibroblast growth factors. It has been shown to regulate many cellular functions including cell proliferation, migration, and differentiation, as well as angiogenesis in a variety of tissues, including skin, blood vessel, muscle, adipose, tendon/ligament, cartilage, bone, tooth, and nerve.
Both FGF2 and oxytocin are unstable and degrade rapidly at room temperature. It has been shown the reconstituted FGF2 solutions are stable for only about one week at 4 ℃ and data shows that oxytocin cannot tolerate being stored at 30°C for more than one month or 2 weeks at 40°C. The aim of this project was to enhance the thermal stability of oxytocin and do preliminary studies on FGF2 in aqueous solutions, which could improve the products shelf-lives.
D-(+)-glucosamine hydrochloride, tetraethyleneglycol (4EG), N-acetyl-D-glucosamine and the mixture of these additives were tested on the stability of oxytocin and FGF2. Our findings showed that all these additives had destabilizing effect on FGF2 stability in PBS. Tetraethylene glycol and D-(+)- glucosamine hydrochloride had a destabilizing effect on oxytocin in both phosphate buffer and acetate buffer. N-acetyl-D-glucosamine showed a negligible or possibly slight improvement to the stability of oxytocin.
The effect of trehalose on stability of FGF2 and oxytocin in aqueous buffer solutions was also tested. Although trehalose showed small to negligible effect on oxytocin stability even at a concentration of 1.0 M in acetate buffer, it slowed down the degradation rate of FGF2 in the presence of all buffers used (HEPES, TRIS, citrate/phosphate and PBS).
The effect of different buffers was evaluated as well. Oxytocin was found to be more stable in acetate buffer than citrate/phosphate buffer or phosphate buffer and we found that the stability is also concentration dependent with acetate buffer concentrations of 0.025 M or less being more beneficial. FGF2 showed the most stablility in PBS buffer compared with the other buffers used.
The effect of crown ethers on the stability of oxytocin and FGF2 in aqueous solution was also explored. 18-crown-6 and 12-crown-4 had destabilizing effect on FGF2. We explored that while 12-crown-4 and 15-crown-5 did not stabilize oxytocin, 18-crown-6 showed to enhance significantly oxytocin stability in citrate/phosphate buffer at pH 4.5. However, in acetate buffer at the same pH, the presence of 18-crown-6 had a destabilizing effect, possibly leading to a different degradation pathway.
The effect of antioxidants such as uric acid, butylated hydroxytoluene, and L-ascorbic acid was also tested on oxytocin stability in solution. Despite known degradation pathways of oxytocin including oxidation of certain amino acids, the antioxidants uric acid and butylated hydroxytoluene had negligible effect on the oxytocin stability while L-ascorbic acid led to significantly faster degradation.
The effect of different pH on FGF2 stability in citrate/phosphate buffer at a pH range (6-8) and acetate buffer at pH 4.5 and 5.5 showed that like other FGF family members, FGF2 is more stable in near-neutral to basic pH compared with acidic pH.Oxýtósin er legæða taugapeptíð sem Alþjóðaheilbrigðismálastofnunin ráðleggur að sé
notað sem fyrsta stigs vörn til að fyrirbyggja og meðhöndla blæðingar eftir fæðingu.
Blæðingar eftir fæðingu eru aðal dánarorsök mæðra (27.1%) í mörgum löndum þar sem
tekjur eru lægri. Basíski fibroblast vaxtaþátturinn (FGF2) er hluti af fjölskyldu fibroblast
vaxtaþátta. Það tekur þátt í að stýra ýmissi frumustarfsemi, þar á meðal frumufjölgun,
flæði, aðgreiningar, sem og æðamyndunar í ýmsum vefjum svo sem húð, æðum, vöðvum,
figu, sinum/liðböndum, brjóski, bein, tennum og taugum.
Bæði FGF2 og oxýtósin eru óstöðug og brotna hratt niður við stofuhita. Sýnt hefur
verið fram á að FGF2 vatnslausnir eru einungis stöðugar í um viku við 4°C og gögn hafa
sýnt að oxýtósin þolir ekki geymsu við 30°C í meira en mánuð eða 2 vikur við 40°C.
Markmið þessa verkefnis var að auka hitastöðugleika oxýtósins og gera frumrannsóknir á
FGF2 í vatnslausnum til að auka geymsluþol þessara efna.
D-(+)-glúkósamín hýdróklóríð, tetraetýlenglýkól (4EG), N-acetýl-D-glúkósamín og
blanda af þessum viðbótarefnum voru prófuð til að sjá áhrif þeirra á stöðugleika oxýtósins
og FGF2. Niðurstöður okkar sýna að öll þessara efna gerðu FGF2 óstöðugra í fosfat buffer
salín (PBS) lausn. 4EG og D-(+) glúkósamín hýdroklóríð gerðu oxýtósin óstöðugra í bæði
fosfat og asetat stuðpúðalausnum. N-acetýl-D-glúkósamín sýndi hverfandi eða hugsanlega
örlítið stöðgandi áhrif á oxýtósin.
Áhrif trehalósa á stöðugleika FGF2 og oxýtósins í vatns stuðpúðalausnum var líka
prófað. Þrátt fyrir að trehalósi sýndi lítil sem hverfandi áhrif á stöðugleika oxýtósin jafnvel
við allt að 1,0 M styrk í asetat stuðpúðalausn, þá hægði það á niðurbrotshraða FGF2 í
viðurvist allar stuðpúðalausnanna sem voruð notaðir (HEPES, TRIS, sítrate/fosfat og
PBS).
Áhrif mismunandi stuðpúðalausna voru líka metin. Oxýtósin reyndist vera stöðugra í acetat
stuðpúðalausn heldur en sítrat/fosfat eða fosfat stuðpúðalausn og við sáum að
stöðugleikinn er líka stykháður, þar sem asetat stuðpúðalausnir með styrk 0,025 M eða
lægra er betra. FGF2 var stöðugast í PBS í samanburði við aðra stuðpúða sem voru notaðir.
Áhrif kórónuetera á stöðugleika oxýtósins og FGF2 í vatnslausnum var líka kannað.
18-kóróna-6 og 12-kóróna-4 höfðu neikvæð áhrif á stöðugleika FGF2. Við sáum að á meðan 12-kóróna-4 og 15-kóróna-5 höfðu ekki stöðgandi áhrif á oxýtósin, þá hafði 18-
kóróna-6 stöðgandi áhrif á óxýtósin í sítrate/fosfat stuðpúðalausn við pH 4,5. Hins vegar
hafði viðurvist 18-kóróna-6 neikvæð áhrif á stöðugleikann í asetat stuðpúðalausn við sama
pH, og leiddi mögulega til annars niðurbrotsferlis.
Áhrif andoxunarefna, svo sem þvagsýru, bútýlað hýdroxýtóluen (BHT) og Lascorbic sýru var líka prófað fyrir stöðugleika oxýtósins í lausn. Þrátt fyrir að þekktar
niðurbrotsleiðir fyrir oxýtósin innihaldi oxun á ákveðnum amínósýrum, þá höfðu
andoxunarefnin þvagsýra og BHT hverfandi áhrif á stöðugleika oxýtósins á meðan Lascorbic sýran leiddi til hraðara niðurbrots.
Áhrif mismunandi sýrustiga á stöðugleika FGF2 í sítrat/fosfat stuðpúðalausn við pH
6-8 og asetat stuðpúðalausn við pH 4,5 og 5,5 sýndi að líkt og önnur prótín í FGF
fjölskyldunni, þá er FGF2 stöðugra við sýrustig sem er nálægt hlutlausu eða örlítið basískt
í samanburði við súrt pH.Tækniþróunarsjóður, project No.:
164072 and Calor eh
Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Get PDF“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Get PDFWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Dispelling the Myths Behind First-author Citation Counts
Get PDFWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
koamabayili/VECTRON-author-checklist: VECTRON author checklist
No full textWe have done our best to complete the author checklist relating to the use of animals in the hut study. Note that the objective for the hut study was to evaluate the IRS treatment applications for residual efficacy against Anopheles mosquitoes, including the local An. coluzzii mosquito population. Cows were only used to attract mosquitoes into the huts and no tests were carried out directly on the cows. The author checklist is intended for use with studies where experiments are carried out on animals, which is why we have had such difficulty in completing this for the hut study, as many of the questions do not relate to how the cows were used
Author-wise bibliometric analysis based on entropy.
No full textAuthor-wise bibliometric analysis based on entropy.</p
Author Under Sail The Imagination of Jack London, 1893-1902
No full textIn Author Under Sail, Jay Williams offers the first complete literary biography of Jack London as a professional writer engaged in the labor of writing. It examines the authorial imagination in London's work, the use of imagination in both his fiction and nonfiction, and the ways he defined imagination in the creative process in his business dealings with his publishers, editors, and agents. In this first volume of a two-volume biography, Williams traverses the years 1893 to 1902, from London's "Story of a Typhoon" to The People of the Abyss. The Jack London who emerges in the pages of Author Under Sail is a writer whose partnership with publishers, most notably his productive alliance with George Brett of Macmillan, was one of the most formative in American literary history. London pioneered many author models during the heyday of realism and naturalism, blurring the boundaries of these popular genres by focusing on absorption and theatricality and the representation of the seen and unseen. London created an impassioned, sincere, and extremely personal realism unlike that of other American writers of the time. Author Under Sail is a literary tour de force that reveals the full range of London as writer, creative citizen, and entrepreneur at the same time it sheds light on the maverick side of machine-age literature.Intro -- Title Page -- Copyright Page -- Dedication -- Contents -- Acknowledgments -- Introduction -- 1. Spirit Truth -- 2. From Absorption to Theatricality and Back Again -- 3. "I Will Build a New Present" -- 4. Sons as Authors -- 5. Fathers as Publishers -- 6. The Daughter as Author -- 7. Lovers as Authors -- 8. At Sea with the Family -- 9. Yellow News, Yellow Stories -- 10. The Return Home -- Notes -- Bibliography -- Index -- About Jay WilliamsIn Author Under Sail, Jay Williams offers the first complete literary biography of Jack London as a professional writer engaged in the labor of writing. It examines the authorial imagination in London's work, the use of imagination in both his fiction and nonfiction, and the ways he defined imagination in the creative process in his business dealings with his publishers, editors, and agents. In this first volume of a two-volume biography, Williams traverses the years 1893 to 1902, from London's "Story of a Typhoon" to The People of the Abyss. The Jack London who emerges in the pages of Author Under Sail is a writer whose partnership with publishers, most notably his productive alliance with George Brett of Macmillan, was one of the most formative in American literary history. London pioneered many author models during the heyday of realism and naturalism, blurring the boundaries of these popular genres by focusing on absorption and theatricality and the representation of the seen and unseen. London created an impassioned, sincere, and extremely personal realism unlike that of other American writers of the time. Author Under Sail is a literary tour de force that reveals the full range of London as writer, creative citizen, and entrepreneur at the same time it sheds light on the maverick side of machine-age literature.Description based on publisher supplied metadata and other sources.Electronic reproduction. Ann Arbor, Michigan : ProQuest Ebook Central, YYYY. Available via World Wide Web. Access may be limited to ProQuest Ebook Central affiliated libraries
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