Computer modelling studies on the mechanism of action of ribonuclease T1

The mechanism of action of ribonuclease (RNase) T1 is still a matter of considerable debate as the results of x-ray, 2-D nmr and site-directed mutagenesis studies disagree regarding the role of the catalytically important residues. Hence computer modelling studies were carried out by energy minimisation of the complexes of RNase T1 and some of its mutants (His40Ala, His40Lys, and Glu58Ala) with the substrate guanyl cytosine (GpC), and of native RNase T1 with the reaction intermediate guanosine 2',3'-cyclic phosphate (G greater than p). The puckering of the guanosine ribose moiety in the minimum energy conformer of the RNase T1-GpC (substrate) complex was found to be O4'-endo and not C3'-endo as in the RNase T1-3'-guanylic acid (inhibitor/product) complex. A possible scheme for the mechanism of action of RNase T1 has been proposed on the basis of the arrangement of the catalytically important amino acid residues His40, Glu58, Arg77, and His92 around the guanosine ribose and the phosphate moiety in the RNase T1-GpC and RNase T1-G greater than p complexes. In this scheme, Glu58 serves as the general base group and His92 as the general acid group in the transphosphorylation step. His40 may be essential for stabilising the negatively charged phosphate moiety in the enzyme-transition state complex.

Poetics of the Nameless Middle : Japan and the West in Philosophy and Music of the Twentieth Century

This study investigates the affinities between philosophy, aesthetics, and music of Japan and the West. The research is based on the structuralist notion (specifically, on that found in the narratology of Algirdas Julius Greimas), that the universal grammar functions as an abstract principle, underlying all kinds of discourse. The study thus aims to demonstrate how this grammar is manifested in philosophical, aesthetic, and musical texts and how the semiotic homogeneity of these texts can be explained on this basis. Totality and belongingness are the key philosophical concepts presented herein. As distinct from logocentrism manifested as substantializations of the world of ideas , god or mind, which was characteristic of previous Western paradigms, totality was defined as the coexistence of opposites. Thus Heidegger, Merleau-Ponty, Dōgen, and Nishida often illustrated it by identifying fundamental polarities, such as being and nothing, seer and seen, truth and illusion, etc. Accordingly, totality was schematically presented as an all-encompassing middle of the semiotic square. Similar values can be found in aesthetics and arts. Instead of dialectic syntagms, differentiated unity is considered as paradigmatic and the study demonstrates how this is manifested in traditional Japanese and Heideggerian aesthetics, as well as in the aspects of music of Claude Debussy and Tōru Takemitsu.

Modes of binding of guanosine monophosphates to ribonuclease T1 - A computer modelling study

Computer-modelling studies on the modes of binding of the three guanosine monophosphate inhibitors 2'-GMP, 3'-GMP, and 5'-GMP to ribonuclease (RNase) T1 have been carried out by energy minimization in Cartesian-coordinate space. The inhibitory power was found to decrease in the order 2'-GMP > 3'-GMP > 5'-GMP in agreement with the experimental observations. The ribose moiety was found to form hydrogen bonds with the protein in all the enzyme-inhibitor complexes, indicating that it contributes to the binding energy and does not merely act as a spacer between the base and the phosphate moieties as suggested earlier. 2'-GMP and 5'-GMP bind to RNase T1 in either of the two ribose puckered forms (with C3'-endo more favoured over the C2'-endo) and 3'-GMP binds to RNase T1 predominantly in C3'-endo form. The catalytically important residue His-92 was found to form hydrogen bond with the phosphate moiety in all the enzyme-inhibitor complexes, indicating that this residue may serve as a general acid group during catalysis. Such an interaction was not found in either X-ray or two-dimensional NMR studies.

Computer simulation of multi-elemental fusion reactor materials

Thermonuclear fusion is a sustainable energy solution, in which energy is produced using similar processes as in the sun. In this technology hydrogen isotopes are fused to gain energy and consequently to produce electricity. In a fusion reactor hydrogen isotopes are confined by magnetic fields as ionized gas, the plasma. Since the core plasma is millions of degrees hot, there are special needs for the plasma-facing materials. Moreover, in the plasma the fusion of hydrogen isotopes leads to the production of high energetic neutrons which sets demanding abilities for the structural materials of the reactor. This thesis investigates the irradiation response of materials to be used in future fusion reactors. Interactions of the plasma with the reactor wall leads to the removal of surface atoms, migration of them, and formation of co-deposited layers such as tungsten carbide. Sputtering of tungsten carbide and deuterium trapping in tungsten carbide was investigated in this thesis. As the second topic the primary interaction of the neutrons in the structural material steel was examined. As model materials for steel iron chromium and iron nickel were used. This study was performed theoretically by the means of computer simulations on the atomic level. In contrast to previous studies in the field, in which simulations were limited to pure elements, in this work more complex materials were used, i.e. they were multi-elemental including two or more atom species. The results of this thesis are in the microscale. One of the results is a catalogue of atom species, which were removed from tungsten carbide by the plasma. Another result is e.g. the atomic distributions of defects in iron chromium caused by the energetic neutrons. These microscopic results are used in data bases for multiscale modelling of fusion reactor materials, which has the aim to explain the macroscopic degradation in the materials. This thesis is therefore a relevant contribution to investigate the connection of microscopic and macroscopic radiation effects, which is one objective in fusion reactor materials research.

Making Music, Making Muslims : A Case Study of Islamic Hip Hop and the Discursive Construction of Muslim Identities on the Internet

Hip-hopin juuret juontavat 1970-luvulle Yhdysvaltoihin, mutta hip-hop-kulttuuri ja musiikkityyli ovat sen jälkeen levinneet ympäri maailmaa osana globalisaatiokehitystä. Myös monet nuoret muslimit tekevät nykyään hip-hop-musiikkia, ja yhä useampi tuo myös sanoituksiinsa vaikutteita Islamista ja elämästään muslimina. Musiikin asema on islamissa varsin kiistelty, eikä sitä ole selvästi sallittu (halal) tai kielletty (haram) muslimeilta. Muslimien tekemää hip-hoppia on toistaiseksi tutkittu hyvin vähän. Tutkielmassa tarkastellaan diskurssianalyysin keinoin, miten tapaustutkimuksena toimivalla muslimhiphop.com-internetsivustolla argumentoidaan ja konstruoidaan käsityksiä muslimi-identiteetistä. Teoreettisena ja analyyttisenä viitekehyksenä toimii sosiaalikonstruktivistinen näkemys identiteetistä kontekstisidonnaisena sekä puheessa ja teksteissä diskursiivisesti rakentuvana. Tutkielma kyseenalaistaa aiempien tutkimusten oletuksen hip-hopista vaikutuksiltaan yksinomaan positiivisena muslimi-identiteetille sekä muslimeja yhdentävänä tekijänä. Aineisto on kerätty edellä mainitulta sivustolta syksyn 2010 ja kevään 2011 aikana, josta analyysiin on rajattu vain itse sivusto ja sen hip-hoppia käsittelevät osiot. Sivusto ja sen perustaja ovat yhdysvaltalaisia, mutta sivustolla esiteltävien artistien tausta on hyvin monikulttuurinen. Moni on myös maahanmuuttajana nykyisessä kotimaassaan. Aineistossa esiintyviä teemoja ja diskursseja eritellään ja analysoidaan tutkielmassa lainauksien avulla. Sivuston periaatteissa ja artistien esillepääsyn kriteereissä määritellään tarkasti asennoituminen Islamin ja musiikin yhdistämiseen: mikäli sanoitukset ja artistit noudattavat Islamin oppeja, on muslimin sallittua tehdä ja kuunnella tällaista musiikkia. Islam-aiheisen hip-hopin perustellaan olevan ennen kaikkea vaihtoehto valtavirran hip-hopille, jota konstruoidaan aineistossa moraalisesti arveluttavaksi. Hip-hopille sekä muslimeille sallittuja ja kiellettyjä elementtejä erottelevan halal-haram-diskurssin ohella aineistosta nousee esiin opetusdiskurssi. Muslimien tekemän hip-hopin perustellaan edistävän Islamin opettamista erityisesti nuorille muslimeille ja siten vahvistavan positiivista muslimi-identiteettiä. Myös positiivisen muutoksen diskurssia käytetään aineistossa runsaasti liittyen mm. muslimiyhteisöihin sekä muslimeihin kohdistuviin taloudellisiin ja sosiaalipoliittisiin epäkohtiin ja stereotypioihin; musiikin sisältöä ja sen tekemistä perustellaan sen voimalla muuttaa asioita parempaan suuntaan. Monet muslimiartistit kamppailevat yhdistääkseen toisaalta Islamin ja taiteellisen luovuuden ja ilmaisuvapauden, toisaalta menestyäkseen kaupallisesti unohtamatta uskonnollista vakaumustaan. Monilla heistä hip-hop on ollut vahvasti läsnä kasvuympäristössä, mutta sen yhdistäminen Islamin periaatteisiin aiheuttaa kysymyksiä ja kyseenalaistuksia oman musiikillisen ja uskonnollisen identiteetin muodosta ja sisällöstä. Aineiston perusteella monet muslimiartistit ja Islam-aiheista hip-hoppia kuuntelevat muslimit joutuvat jatkuvasti puolustamaan musiikkia siihen kielteisesti suhtautuville muslimeille sekä ei-muslimeille, jotka vierastavat sen uskonnollisuutta. Muslimi-identiteettiä neuvotellaan jatkuvasti, ja se näyttäytyy aineistossa moniulotteisena ja tilanteisesti rakentuvana. Avainsanat: Muslimit, Islam, hip-hop, identiteetti, Internet, diskurssi, diskurssianalyysi

Computer modelling studies of ribonuclease A-pyrimidine nucleotide complexes

Different modes of binding of pyrimidine monophosphates 2'-UMP, 3'-UMP, 2'-CMP and 3'-CMP to ribonuclease (RNase) A are studied by energy minimization in torsion angle and subsequently in Cartesian coordinate space. The results are analysed in the light of primary binding sites. The hydrogen bonding pattern brings out roles for amino acids such as Asn44 and Ser123 apart from the well known active site residues viz., His12,Lys41,Thr45 and His119. Amino acid segments 43-45 and 119-121 seem to be guiding the ligand binding by forming a pocket. Many of the active site charged residues display considerable movement upon nucleotide binding.

Computer modeling studies on the binding of 2',5'-linked dinucleoside phosphates to ribonuclease T1-influence of subsite interactions on the substrate specificity

The modes of binding of Gp(2',5')A, Gp(2',5')C, Gp(2',5')G and Gp(2',5')U to RNase T1 have been determined by computer modelling studies. All these dinucleoside phosphates assume extended conformations in the active site leading to better interactions with the enzyme. The 5'-terminal guanine of all these ligands is placed in the primary base binding site of the enzyme in an orientation similar to that of 2'-GMP in the RNase T1-2'-GMP complex. The 2'-terminal purines are placed close to the hydrophobic pocket formed by the residues Gly71, Ser72, Pro73 and Gly74 which occur in a loop region. However, the orientation of the 2'-terminal pyrimidines is different from that of 2'-terminal purines. This perhaps explains the higher binding affinity of the 2',5'-linked guanine dinucleoside phosphates with 2'-terminal purines than those with 2'-terminal pyrimidines. A comparison of the binding of the guanine dinucleoside phosphates with 2',5'- and 3',5'-linkages suggests significant differences in the ribose pucker and hydrogen bonding interactions between the catalytic residues and the bound nucleoside phosphate implying that 2',5'-linked dinucleoside phosphates may not be the ideal ligands to probe the role of the catalytic amino acid residues. A change in the amino acid sequence in the surface loop region formed by the residues Gly71 to Gly74 drastically affects the conformation of the base binding subsite, and this may account for the inactivity of the enzyme with altered sequence i.e., with Pro, Gly and Ser at positions 71 to 73 respectively. These results thus suggest that in addition to recognition and catalytic sites, interactions at the loop regions which constitute the subsite for base binding are also crucial in determining the substrate specificity.