Synthesis of triplex-forming oligonucleotide conjugates of the anticancer drug temodal

Covalent attachment of the anticancer drugs temozolomide (Temodal) and mitozolomide to triplex-forming oligonucleotides (TFOs) is a potential way of targeting these alkylating agents to specific gene sequences to maximise site-selectivity. In this work, polypyrimidine TFO conjugates of both drugs were synthesised and targeted to duplex DNA in an attempt to effect site-specific alkylation of guanine residues. Concurrently, in an attempt to enhance the triple helix stability of TFOs at neutral pH, the thermal stabilities of triplexes formed from TFOs containing isoguanine, 2-O-benzyl- and 2-O-allyl-adenine were evaluated. A novel cleavage and deprotection procedure was developed which allowed for the solid phase synthesis of the base-sensitive TFO-drug conjugates using a recently developed silyl-linked controlled pore glass (SLCPG) support. Covalent attachment of either temozolomide or mitozolomide at the 5'-end of TFO conjugates caused no destabilisation of the triplexes studied. The synthesis of a phosphoramidite derivative of mitozolomide enabled direct incorporation of this reagent into a model sequence during DNA synthesis. After cleavage and deprotection of the TFO-drug conjugate, the 5'-end mitozolomide residue was found to have decomposed presumably as a result of ring-opening of the tetrazinone ring. The base-sensitive antibacterial and antitumour agent, metronidazole, was also successfully incorporated at the 5'-end of the oligonucleotide d(T8) using conventional methods. Two C2-substituted derivatives of 2'-deoxyadenosine containing 2-O-benzyl and 2-O-allyl groups were synthesised. Hydrogenolysis of the 2-O-benzyl analogue provided a useful route, amenable to scale-up, for the synthesis of the rare nucleoside 2'-deoxyisoguanosine (isoG). Both the 2-O-allyl and 2-O-benzyl derivatives were incorporated into TFO sequences using phosphoramidite methodology. Thermal melting experiments showed that the 2-O-allyl and 2-O-benzyl groups caused marked destabilisation of the triple helices studied, in contrast to hexose-DNA duplexes, where aralkyl substituents caused significant stabilisation of duplexes. TFOs containing isoG were synthesised by Pd(O)-catalysed deallylation of 2-0-allyl adenine residues. These sequences containing isoG, in its N3- or 02-H tautomeric form, formed triple helices which were equally as stable as those containing adenine.

On the Time Complexity of the Problem Related to Reducts of Consistent Decision Tables

In recent years, rough set approach computing issues concerning reducts of decision tables have attracted the attention of many researchers. In this paper, we present the time complexity of an algorithm computing reducts of decision tables by relational database approach. Let DS = (U, C ∪ {d}) be a consistent decision table, we say that A ⊆ C is a relative reduct of DS if A contains a reduct of DS. Let s = d} , F> be a relation schema on the attribute set C ∪ {d}, we say that A ⊆ C is a relative minimal set of the attribute d if A contains a minimal set of d. Let Qd be the family of all relative reducts of DS, and Pd be the family of all relative minimal sets of the attribute d on s. We prove that the problem whether Qd ⊆ Pd is co-NP-complete. However, the problem whether Pd ⊆ Qd is in P .

Consumer (dis)satisfaction response to disconfirmation: An examination of the form and the underlying process

The purpose of this dissertation was to examine the form of the consumer satisfaction/dissatisfaction (CS/D) response to disconfirmation. In addition, the cognitive and affective processes underlying the response were also explored. ^ Respondents were provided with information from a prior market research study about a new brand of printer that was being tested. This market research information helped set prior expectations regarding the print quality. Subjects were randomly assigned to an experimental condition that manipulated prior expectations to be either positive or negative. Respondents were then provided with printouts that had performance quality that was either worse (negative disconfirmation) or better (positive disconfirmation) than the prior expectations. In other words, for each level of expectation, respondents were assigned to either positive or negative disconfirmation condition. Subjects were also randomly assigned to a condition of either a high or low level of outcome involvement. ^ Analyses of variance indicated that positive disconfirmation led to a more intense CS/D response than negative disconfirmation, even though there was no significant difference in the intensity for positive and negative disconfirmation. Intensity of CS/D was measured by the distance of the CS/D rating from the midpoint of the scale. The study also found that although outcome involvement did not influence the polarity of the CS/D response, the more direct measures of processing involvement such as the subjects' concentration, attention and care in evaluating the printout did have a significant positive effect on CS/D intensity. ^ Analyses of covariance also indicated that the relationship between the intensity of the CS/D response and the intensity of the disconfirmation was mediated by the intensity of affective responses. Positive disconfirmation led to more intense affective responses than negative disconfirmation. ^

Clovis-le-Grand, premier roi chrétien, fondateur de la monarchie française;

Mode of access: Internet.

Clovis, tragédie en cinq actes, précéd��e de consid��rations historiques;

Mode of access: Internet.

[Archives de la Parole]. , [The king and the margosa seed] : récit en dravidien, telugu, Province de Madras / [Sir George Grierson], éd. ; Linguistic survey of India ; [V. Krishna Rao], voix

[Traditions. Asie. Inde. Présidence de Madras [i.e. Chennai]. Ceded Districts]

[Archives de la Parole]. , [The king and the margosa seed] : récit en dravidien, telugu, Province de Madras / [Sir George Grierson], éd. ; Linguistic survey of India ; [K. Divakara Rao], voix

[Traditions. Asie. Inde. Présidence de Madras [i.e. Chennai]. Ceded Districts]

[Archives de la Parole]. , The daughter of the king of flowers : a fable in Kodaku from Surguja (C.P.) [i.e. Central Provinces] / [Sir George Grierson], éd. ; Linguistic survey of India ; [Jūthan Koḍākū], voix

[Traditions. Asie. Inde. Madhya Pradesh. Chhattisgarh]

King Horn : with fragments of Floriz and Blancheflur, and of the Assumption of Our Lady : from a MS (GG. 4.27.2) in the Cambridge University Library : also from MSS. in the British Museum The Assumption of Our Lady (A.D. MSS. 10036), and Fragments of the Floyres and Blanchefleur (Cotton Vitelluis D.111) /

Includes glossarial index.

Itinerary of King Edward the First throughout his reign, A. D. 1272-1307, exhibiting his movements from time to time, so far as they are recorded.

Mode of access: Internet.

The voyages and travells of the ambassadors sent by Frederick Duke of Holstein, to the Great Duke of Muscovy, and the King of Persia : begun in the year M.DC.XXXIII, and finish'd in M.DC.XXXIX : containing a compleat history of Muscovy, Tartary, Persia, and other adjacent countries : with several publick transactions reaching near the present times : in VII books ;

Mode of access: Internet.

The life of Marguerite d'Angouleme, Queen of Navarre, Duchesse d'Alencon and de Berry, sister of Francis I., King of France : From numerous unpublished sources, including MS. documents in the Bibliotheque Imperiale, and the Archives du Royaume de France, and also the private correspondence of Queen Marguerite with Francis I., & c.

Mode of access: Internet.

Certain sermons or homilies appointed to be read in churches in the time of Queen Elizabeth; and reprinted by authority from King James I., A.D. 1623. To which are added the constitutions and canons of the Church of England, set forth A.D. 1603. With an appendix, containing the articles of religion, constitution, and canons of the Protestant Episcopal Church in the United States of America.

Mode of access: Internet.

The life of Samuel Johnson, D.D. : the first president of King's College, in New York. Containing many interesting anecdotes; a general view of the state of religion and learning in Connecticut during the former part of the last century; and an account of the institution and rise of Yale College, Connecticut; and of King's (now Columbia) College, New-York /

Microfilm. Ann Arbor, Mich., University Microfilms [n.d.] (American culture series, Reel 257.3)