Semikarbazon – svestrani farmakofor u dizajniranju antikonvulziva

During the last fifteen years semicarbazones have been extensively investigated for their anticonvulsant properties. 4-(4-Flurophenoxy) benzaldehyde semicarbazone (C0102862, V102862) has been discovered as a lead molecule and is being developed as a potent antiepileptic drug, with maximal electroskock (MES) ED50 (i.p. 12.9 mg kg1). In MES (oral screen), this compound has protective index (PI = TD50/ED50 >315) higher than carbamazepine (PI 101), phenytoin (PI >21.6) and valproate (PI 2.17). This compound is a potent sodium channel blocker. Other semicarbazones have demonstrated activity in various chemoshock screens, like subcutaneous pentylenetetrazole (ScPTZ), subcutaneous strychnine (ScSTY), subcutaneous picrotoxine (ScPIC) and subcutaneous bicculline (ScBIC). Semicarbazones are also GABA-transaminase inhibitors. Extensive structure-activity relationship has demonstrated that F, Cl, Br and NO2 substitutents in the arylhydrophobic pocket and a hydrogen bonding domain (HBD) are generally found in active anticonvulsant agents.Tijekom posljednjih petnaest godina intenzivno su istraživana antikonvulzivna svojstva semikarbazona. 4-(4-Flurofenoksi)benzaldehid semikarbazon (C0102862, V102862) otkriven je kao vodeći spoj iz kojeg je razvijen antiepileptik s maksimalnom elektrošok aktivnošću (MES) ED50 12,9 mg kg1 (i.p.) i zaštitnim indeksom (PI = TD50/ED50 > 315) većim od karbamazepina (PI 101), fenitoina (PI > 21,6) i valproata (PI 2,17). Spoj je snažni blokator natrijevih kanala. Drugi su se semikarbazoni pokazali učinkovitima u različitim kemo-šok testovima, kao što su supkutana primjena pentilentetrazola, strihnina, pikrotoksina i bikukulina. Semikarbazoni su također inhibitori GABA-transaminaze. Opširne studije odnosa strukture i djelovanja pokazale su da je za antikonvulzivno djelovanje bitna prisutnost F, Cl, Br i NO2 supstituenata u arilhidrofobnom džepu i domena za vezanje vodikovim vezama (HBD)

The Absurdity of Hinduism: Gandhi’s Ideas on Religion and Truth

This paper seeks to provide a renewed meaning to the idea of truth by enclosing it within Gandhi’s rhetorical use of the term religion. The religion that he seeks to present to us as Hinduism is absurd on all fronts, it is argued here. It is through such absurdity that he infuses notions of validity and obeyance on his own terms to take us to profuse criticisms of not only colonial but civilizational modernity as well. Further a newer meaning is given to Hinduism in a rather unexpected manner even in the context of the Indian national movement. The point about political conservatism, the element of exoticism and God takes us to adventures around truth by a thinker-activist speaking as a colonial subject.  &nbsp

Variable Selection in Accelerated Failure Time (AFT) Frailty Models: An Application of Penalized Quasi-Likelihood

Variable selection is one of the standard ways of selecting models in large scale datasets. It has applications in many fields of research study, especially in large multi-center clinical trials. One of the prominent methods in variable selection is the penalized likelihood, which is both consistent and efficient. However, the penalized selection is significantly challenging under the influence of random (frailty) covariates. It is even more complicated when there is involvement of censoring as it may not have a closed-form solution for the marginal log-likelihood. Therefore, we applied the penalized quasi-likelihood (PQL) approach that approximates the solution for such a likelihood. In addition, we introduce an adaptive penalty function that makes the selection on both fixed and frailty effects in a left-censored dataset for a parametric AFT frailty model. We also compared our penalty function with other established procedures via their performance on accurately choosing the significant coefficients and shrinking the non-significant coefficients to zero

Optical studies on diamond surfaces

A brief review of the existing information on diamonds, including their physical properties and characteristic growth and solution features, is given in Part I. Part II deals with a short account of all the experimental techniques used in the present optical and interferometric studies of the microstructures of diamonds. Although Octahedron diamonds occur more frequently than the dodecahedron, yet in some mines the dodecahedron diamonds dominate not only in quantity but also in size. This fact is not consistent with the commonly accepted view that the dodecahedron form has developed due to the solution of Octahedron faces. It is expected that the present investigations on the microstructures of diamonds will throw some light on the conditions of their growth. The microstructures of dodecahedron diamonds are classified under two headings, namely (i) rare type of microstructures and (ii) common type of microstructures. Part III deals with the rare type of microstructures and in Chapter 3 are described unusual circular patterns which have been observed on three dodecahedral diamonds. Certain circular features which were illustrated by Sutton in 1928 with pencilled drawings resemble those described here. These features consist of slightly raised circular discs usually placed eccentrically one over the other and at times are overlapping and intersecting each other. The origin of these features has been discussed and their formation is attributed to a mechanism in which it is shown that liquid or gaseous bubbles were sticking on the faces of the crystal whilst the dissolution of the dodecahedral faces was taking place everywhere excepting the regions which were protected by the bubbles. Chapter IV deals with a brief review of the etch methods and the information on artificial etching of diamonds. Natural etch patterns not observed previously on the dodecahedron diamonds are also described in this Chapter. According to the experimental evidence these etch pits are expected to be canoe-shaped and perpendicular to the longer diagonal of the rhombic face. However, the natural etch pits are (a) canoe-shaped (b) oblong-shaped and (c) oval-shaped. The deviation in shape of these etch pits and their occurrence is explained. These natural etch pits uniquely arrange themselves in circular arrays and this has been attributed to the formation of liquid bubbles on the surface before natural etching started. Common microstructures of dodecahedral faces of diamonds as observed are (i) striations (ii) irregular network and (iii) rectilinear parallelogram network. It is suggested that the striations and irregular network owe their existence to growth and that subsequent solution of the faces reveals these features. The rectilinear parallelogram network is considered to be due to the solution of the faces of diamond which shows up those (111) planes along which diamond grows. These (111) planes are those which intersect (110) faces normally. The study of common microstructures of dodecahedron diamonds affords a further confirmation of the view that the dodecahedral faces of diamond are much more susceptible to solution than the octahedron faces. In Appendix A, observations made on trigons occurring on the octahedron faces of diamonds are described. The presence of a flat-bottomed trigon whose base is at the same level as a neighbouring area, the occurrence of slip and the presence of growth hills only on octahedron diamonds appears to be conclusive proof that they are growth features. In Appendix B, some graphitization experiments are given and it is concluded that graphitization sets in at a slow a temperature as 1060&deg;C. when diamond is heated in a graphite crucible in an atmosphere of Nitrogen.<p