469 research outputs found

    Vakıfların İmparatorluk Hayatındaki Olumlu ve Olumsuz Etkileri

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    From Shakespeare to Kierkegaard: an Existential Reading of Hamlet

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    Shakespeare'in "Hamlet" oyunu varoluşçuluk felsefesi bağlamında yorumlanabilir. Danimarka'da, kendisini Sartre'in 'boşluk' ('void') olarak nitelendirdigi türde bir ortamda bulan Hamlet, çürümüş bir dünyada mücadele veren modern Avru-pa'lı insan kavramının bir örneği olarak algılanabilir. Hamlet 'bulantısını' ('nausea') yenmeye, insanları maskelerinden ve yanıltıcı görünümlerinden arındırmaya çabalarken Kierkegaard'in betimlediği üç yaşam evresinden geçer:estetik, ahlaki, ve dini. Bu evreler kökenlerinde birbirleriyle çelişki halinde olduklari için, insan temel bir seçim -- 'ya ... ya da' ('either/or')-- yapmak durumundadır. Oyunda Hamlet'in tepkileri ve tepkisizlikleri bu bağlam içinde incelenebilir.Shakespeare's Hamlet yields conveniently to an existential reading. Hamlet may be seen as the prototype of the modern European man who struggles in a "rotten" world. In Denmark, he finds himself in a Sartrean "void". As he struggles to overcome his "nausea" by trying to unmask men, strip them of their fine appearances and show them in their true nature, Hamlet passes through the three stages of life described by Kierkegaard: the aesthetic, the ethical and the religious. Since these stages are in contradiction with one another, there is a basic choice, an "either/or" facing man. Hamlet's actions or non-actions in the play can be studied within the framework of this context

    Samuel Taylor Coleridge’s "The Rime of the Ancient Mariner" and "Christabel" : Doubts About the Universal Order"

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    On dokuzuncu yüzyıl İngiliz romantik şairlerinin yapıtlarında karanlık, kuşkuların, umutsuzluğun ve güvensizliğin egemen olduğu bir yön vardır. Samuel Taylor Coleridge de bu çalışmada ele alınan şiirlerinde evrenin düzenini sağlayan metafizik bir gücün varlığı konusundaki kuşkularını dile getirmektedir. Coleridge'in karabasan dünyasında güven duyulabilecek bir evrensel ve ahlaki düzen yerine tesadüflerin hakim olduğu bir düzensizlik hüküm sürmektedir.There is a dark strain which can be traced in the poetry of all the major nineteenth century English romantic poets: a scepticism about the ultimate purpose of man's life, a sense of having lost a metaphysical certainty and faith in the presence of a benevolent power who maintains harmony and order in the universe. Samuel Taylor Coleridge is one of them. In "The Rime of the Ancient Mariner" and "Christabel", he reveals a nightmarish vision of the universe where moral order seems to be replaced by a cosmic "hap"

    Samuel Taylor Coleridge’s "The Rime of the Ancient Mariner" and "Christabel" : Doubts About the Universal Order"

    Get PDF
    On dokuzuncu yüzyıl İngiliz romantik şairlerinin yapıtlarında karanlık, kuşkuların, umutsuzluğun ve güvensizliğin egemen olduğu bir yön vardır. Samuel Taylor Coleridge de bu çalışmada ele alınan şiirlerinde evrenin düzenini sağlayan metafizik bir gücün varlığı konusundaki kuşkularını dile getirmektedir. Coleridge'in karabasan dünyasında güven duyulabilecek bir evrensel ve ahlaki düzen yerine tesadüflerin hakim olduğu bir düzensizlik hüküm sürmektedir.There is a dark strain which can be traced in the poetry of all the major nineteenth century English romantic poets: a scepticism about the ultimate purpose of man's life, a sense of having lost a metaphysical certainty and faith in the presence of a benevolent power who maintains harmony and order in the universe. Samuel Taylor Coleridge is one of them. In "The Rime of the Ancient Mariner" and "Christabel", he reveals a nightmarish vision of the universe where moral order seems to be replaced by a cosmic "hap"

    Targeted Disruption of Lynx2 Reveals Distinct Functions for Lynx Homologues in Learning and Behavior

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    Endogenous short peptide modulators of ion channels provide a new level of regulation of nervous function. Lynx1 was identified as an endogenous mammalian homologue of snake venom peptide neurotoxins capable of binding to and functionally modulating nicotinic cetylcholine receptors (nAChR). Lynx1 is a member of the Ly6-α−neurotoxin superfamily (Ly6SF) of genes. Through extensive database searches, I identified 85 members of this superfamily including previously unidentified vertebrate and invertebrate family members. I show that these proteins are very divergent in their sequences, and identify two conserved subfamilies, snake toxins and immune system expressed Ly6 genes through phylogenetic inference. I also discovered conserved sequences among Ly6SF proteins additional to the cysteines that characterize the three-dimensional topology of Ly6 domain. From these Ly6SF molecules, I characterize three lynx1 homologues: lynx2, lynx3 and Ly6H. These have different and specific expression patterns in the central and peripheral nervous systems. Importantly, like lynx1, lynx2 and lynx3 are able to bind specific nAChR combinations and modulate their desensitization properties, while Ly6H does not bind nor modulate the function of nAChRs. I have also analyzed the in vivo function of lynx2, through the targeted deletion of lynx2 in mice. Lynx2 null mutant (lynx2-/-) mice exhibited increased anxiety, better associative learning and better motor coordination and learning than wild type (WT) mice. Nicotine and nicotinic receptor antagonist, mecamylamine, show distinct effects on motor learning in lynx2-/- mice and WT mice. The properties of this new family of lynx1-like molecules, taken together with those of lynx1 and the secreted Ly6SF member SLURP1 (secreted Ly6/UPAR related protein), suggest a general role for Ly6SF proteins in the modulation of nAChRs and other receptor proteins

    Targeted Disruption of Lynx2 Reveals Distinct Functions for Lynx Homologues in Learning and Behavior

    Get PDF
    Endogenous short peptide modulators of ion channels provide a new level of regulation of nervous function. Lynx1 was identified as an endogenous mammalian homologue of snake venom peptide neurotoxins capable of binding to and functionally modulating nicotinic cetylcholine receptors (nAChR). Lynx1 is a member of the Ly6-α−neurotoxin superfamily (Ly6SF) of genes. Through extensive database searches, I identified 85 members of this superfamily including previously unidentified vertebrate and invertebrate family members. I show that these proteins are very divergent in their sequences, and identify two conserved subfamilies, snake toxins and immune system expressed Ly6 genes through phylogenetic inference. I also discovered conserved sequences among Ly6SF proteins additional to the cysteines that characterize the three-dimensional topology of Ly6 domain. From these Ly6SF molecules, I characterize three lynx1 homologues: lynx2, lynx3 and Ly6H. These have different and specific expression patterns in the central and peripheral nervous systems. Importantly, like lynx1, lynx2 and lynx3 are able to bind specific nAChR combinations and modulate their desensitization properties, while Ly6H does not bind nor modulate the function of nAChRs. I have also analyzed the in vivo function of lynx2, through the targeted deletion of lynx2 in mice. Lynx2 null mutant (lynx2-/-) mice exhibited increased anxiety, better associative learning and better motor coordination and learning than wild type (WT) mice. Nicotine and nicotinic receptor antagonist, mecamylamine, show distinct effects on motor learning in lynx2-/- mice and WT mice. The properties of this new family of lynx1-like molecules, taken together with those of lynx1 and the secreted Ly6SF member SLURP1 (secreted Ly6/UPAR related protein), suggest a general role for Ly6SF proteins in the modulation of nAChRs and other receptor proteins

    DIETARY INTERACTIONS INFLUENCING FEED INTAKE, NUTRIENT UTILISATION AND APPETITE REGULATION IN THE RAINBOW TROUT, Oncorhynchus mykiss

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    Dietary factors are one of the most significant considerations in the regulation of appetite in fish since dietary nutrient and energy concentration modulate feed intake in the short and longer term. These interactions may also be important from a commercial aspect, since the objective of aquaculture is to obtain maximum growth, feed efficiency and consumer acceptance of the product. This thesis addresses the major dietary components which are likely to influence appetite in rainbow trout. These include dietary lipid level, carbohydrate content and degree of complexity as well as energy density and protein/energy ratio. Experimental data is presented which examines the influence of such factors on reed intake, growth performance, nutrient utilisation, gastric evacuation rate, return of appetite and changes with respect to the postprandial level of circulating plasma metabolites. It is proposed that rainbow trout have the capacity to regulate feed intake within specific constraints. On the other hand, trout become obese when offered high oil diets and fail to control feed intake in the short term, possibly due to the palatability of lipids. Regulation may also appear at a metabolic level following accumulation of lipids in adipose tissue. Gastric evacuation rate was probably the main factor in the short term influencing feed intake. This was irrespective of carbohydrate complexity or level in the diet. However, simple sugars might suppress the appetite of trout in the longer term. The biochemical status of liver via plasma glucose concentration may play a more important role compared to gastric fullness in the long- term regulation of appetite. It was postulated that X-radiography was a paramount technique for the quantification of sequential meals and return of appetite measurements in these investigations. The above parameters and their interactions were studied in relation to the physiological control of feed intake in order to develop a more defined model for such processes and to improve the optimum feeding regimes for rainbow trout under intensive production conditions. This is discussed within the wider concept of fish nutrition, and the implications for future research in this area are stated

    Oligonucleotide delivery with cell surface binding and cell penetrating peptide amphiphile nanospheres

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    Cataloged from PDF version of article.A drug delivery system designed specifically for oligonucleotide therapeutics can ameliorate the problems associated with the in vivo delivery of these molecules. The internalization of free oligonudeotides is challenging, and cytotoxicity is the main obstacle for current transfection vehicles. To develop nontoxic delivery vehicles for efficient transfection of oligonudeotides, we designed a self-assembling peptide amphiphile (PA) nanosphere delivery system decorated with cell penetrating peptides (CPPs) containing multiple arginine residues (R-4 and R-8), and a cell surface binding peptide (KRSR), and report the efficiency of this system in delivering G-3129, a Bcl-2 antisense oligonucleotide (AON). PA/AON (peptide amphiphile/antisense oligonucleotide) complexes were characterized with regards to their size and secondary structure, and their cellular internalization efficiencies were evaluated. The effect of the number of arginine residues on the cellular internalization was investigated by both flow cytometry and confocal imaging, and the results revealed that uptake efficiency improved as the number of arginines in the sequence increased. The combined effect of cell penetration and surface binding property on the cellular internalization and its uptake mechanism was also evaluated by mixing R-8-PA and KRSR-PA. R-8 and R-8/KRSR decorated PAs were found to drastically increase the internalization of AONs compared to nonbioactive PA control. Overall, the KRSR-decorated self-assembled PA nanospheres were demonstrated to be noncytotoxic delivery vectors with high transfection rates and may serve as a promising delivery system for AONs

    Slow release and delivery of antisense oligonucleotide drug by self-assembled peptide amphiphile nanofibers

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    Cataloged from PDF version of article.Antisense oligonucleotides provide a promising therapeutic approach for several disorders including cancer. Chemical stability, controlled release, and intracellular delivery are crucial factors determining their efficacy. Gels composed of nanofibrous peptide network have been previously suggested as carriers for controlled delivery of drugs to improve stability and to provide controlled release, but have not been used for oligonucleotide delivery. In this work, a self-assembled peptide nanofibrous system is formed by mixing a cationic peptide amphiphile (PA) with Bcl-2 antisense oligodeoxynucleotide (ODN), G3139, through electrostatic interactions. The self-assembly of PA-ODN gel was characterized by circular dichroism, rheology, atomic force microscopy (AFM) and scanning electron microscopy (SEM). AFM and SEM images revealed establishment of the nanofibrous PA-ODN network. Due to the electrostatic interactions between PA and ODN, ODN release can be controlled by changing PA and ODN concentrations in the PA-ODN gel. Cellular delivery of the ODN by PA-ODN nanofiber complex was observed by using fluorescently labeled ODN molecule. Cells incubated with PA-ODN complex had enhanced cellular uptake compared to cells incubated with naked ODN. Furthermore, Bcl-2 mRNA amounts were lower in MCF-7 human breast cancer cells in the presence of PA-ODN complex compared to naked ODN and mismatch ODN evidenced by quantitative RT-PCR studies. These results suggest that PA molecules can control ODN release, enhance cellular uptake and present a novel efficient approach for gene therapy studies and oligonucleotide based drug deliver

    Heterotrophic ammonium removal by a novel hatchery isolate Acinetobacter calcoaceticus STB1

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    Cataloged from PDF version of article.A novel bacterial strain, STB1, was isolated from a commercial sea bass hatchery and found to display high heterotrophic ammonium removal characteristics at different concentrations of ammonium (NH4+-N). The species identity of STB1 was determined via 16S rRNA gene sequence analysis to be Acinetobacter calcoaceticus. We evaluated ammonium removal characteristics of STB1 at varying ammonium concentrations, and observed that STB1 can almost completely remove ammonium at low (50 mg l -1), and medium (100 mg l -1) concentrations within 72 h, while 45% ammonium removal was observed at a higher concentration (210 mg l -1) during the same period. Trace amount of the metabolized ammonium was converted to nitrite or nitrate and 22.16% of total nitrogen was incorporated into cell biomass, while 4.34% of total nitrogen was initially incorporated into cell biomass and subsequently released to the supernatant fraction in the 100 mg l -1 sample. Most of the remaining conversion products are expected to be gaseous denitrification products. Toxicological studies with Artemia salina (brine shrimp) nauplii revealed that STB1 strain is non-toxic to Artemia larvae, which suggests that STB1 can be safely and efficiently utilized in water quality enrichment in aquatic ecosystems. © 2012 Elsevier Ltd
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