Analysis of polymorphism at site -174 G/C of interleukin-6 promoter region in multiple myeloma

It is well established that interleukin-6 (IL-6) is an essential growth factor for multiple myeloma (MM) and patients with increased IL-6 levels have a poor prognosis. In healthy subjects, the presence of the C allele at a polymorphic site (-174 G/C) of the IL-6 gene is related to low IL-6 levels. In view of the potential association of this particular polymorphism with IL-6 concentration, and the relevance of IL-6 in MM pathogenesis, the objective of the present study was to investigate the prevalence of IL-6 (-174 G/C) promoter polymorphism and its association with development of MM in Brazilian individuals. We investigated the prevalence of these alleles in 52 patients and 60 healthy subjects (matched by age, sex, and race) of a Brazilian population. Thirty patients were male (42.4%), 24 (46.2%) were white and the median age at diagnosis was 58.5 years (range: 28 to 84 years). To determine the IL-6 (-174 G/C) polymorphism, molecular analysis was performed by polymerase chain reaction followed by endonuclease restriction digestion. The genotype distributions observed in the group of patients were 4% CC, 42% GC and 54% GG. The C allele frequency was 0.25. These results were similar to the control group, suggesting no impact of this polymorphism on the susceptibility to MM.

Probing the SERCA1a sarcoplasmic reticulum Ca2+-ATPase phosphorylation-site mutant D351E with inorganic phosphate

The expression of sarcoplasmic reticulum SERCA1a Ca2+-ATPase wild-type and D351E mutants was optimized in yeast under the control of a galactose promoter. Fully active wild-type enzyme was recovered in yeast microsomal membrane fractions in sufficient amounts to permit a rapid and practical assay of ATP hydrolysis and phosphoenzyme formation from ATP or Pi. Mutant and wild-type Ca2+-ATPase were assayed for phosphorylation by Pi under conditions that are known to facilitate this reaction in the wild-type enzyme, including pH 6.0 or 7.0 at 25ºC in the presence of dimethylsulfoxide. Although glutamyl (E) and aspartyl (D) residue side chains differ by only one methylene group, no phosphoenzyme could be detected in the D351E mutant, even upon the addition of 40% dimethylsulfoxide and 1 mM 32Pi in the presence of 10 mM EGTA and 5 mM MgCl2. These results show that in the D351E mutant, increasing hydrophobicity of the site with inorganic solvent was not a sufficient factor for the required abstraction of water in the reaction of E351 with Pi to form a glutamylphosphate (P-E351) phosphoenzyme moiety. Mutation D351E may disrupt the proposed alignment of the reactive water molecule with the aspartylphosphate (P-D351) moiety in the phosphorylation site, which may be an essential alignment both in the forward reaction (hydrolysis of aspartylphosphate) and in the reverse reaction (abstraction of water upon formation of an aspartylphosphate intermediate).

Developing construction site operations for EPC power plant projects

The purpose of this thesis is to find development areas for site operations in power plant construction projects delivered by Wärtsilä. The inspected operations are subcontractor management, site material management and work scheduling. The contractor's role in EPC project is to respond for engineering, procurement, and construction supervision. Geographical and cultural differences brings challenges for finding development areas as Wärtsilä delivers projects world-wide. Searching for development area is mainly made with survey, which answers were collected from the target company's site personnel. Based on the results, with good planning and preparation various problems would be avoided. An external view for the thesis was collected by an expert interview, which was held to three expe-rienced construction operating executives. Interviewees believed that with the se-lection of right site personnel and clearly defined areas of responsibility will great-ly affect the outcome of the project. Some of the theory has been collected from areas, which have helped to under-stand the inspected operations on site. Improving competence knowledge has been important due to the broad scope of work and the author’s inexperience of the topic. Also generally effective practices from construction projects has been col-lected to the theory part. Functionality of general practices have been reflected together with the results of empirically collected data for Wärtsilä's projects. As a result, a model was generated where development proposals and the benefits from new procedures were presented.

Utilização do Intron Splice Site primer EI-1 na discriminação de leveduras contaminantes do processo de fermentação alcoólica

Neste trabalho, utilizamos o Intron Splice Site primer EI-1 para a análise do perfil de amplificação de diferentes espécies de leveduras consideradas contaminantes no processo de fermentação alcoólica, originadas de uma destilaria no Estado da Paraíba na safra 2004/2005. Foram realizadas as etapas analíticas para discriminação molecular das leveduras a partir da extração do DNA total, amplificação por PCR e análise do perfil genético. Os resultados obtidos indicam que o Intron Splice Site primer EI-1é muito eficaz na discriminação das diferentes espécies de Saccharomyces e não Saccharomyces, evidenciando padrões de bandas específicos para as leveduras analisadas. Este primer, por ser complementar a uma região muito conservada do genoma das leveduras, mostrou-se incapaz de uma discriminação intraespecífica. Isto demonstra a utilidade deste marcador no auxílio à taxonomia de leveduras.

On site measurements of DC link electrolytic capacitor bank of frequency converter using constant DC magnetization of the motor

Preventive maintenance of frequency converters has been based on pre-planned replace-ment of wearing or ageing components. Exchange intervals follow component life-time expectations which are based on empirical knowledge or schedules defined by manufac-turer. However, the lifetime of a component can vary significantly, because drives are used in very different operating environments and applications. The main objective of the research was to provide information on methods, i.e. how in-verter's operating condition can be measured reliably under field conditions. At first, the research focused on critical components such as current transducers, IGBTs and DC link capacitor bank, because these aging have already been identified. Of these, the DC link capacitor measurement method was selected for closer examination. With this method, the total capacitance and its total series resistance can be measured. The suitability of the measuring procedure was estimated on the basis of practical measurements. The research was made by using so called triangulation method, including a literature review, simulations and practical measurements. Based on the results, the new measu-rement method seems suitable with some reservations to practical measurements. How-ever, the measuring method should be further developed in order to improve its reliability.

Incentivising Innovation? The competition law approach to the new challenge clauses in the competition rules for technology licensing agreements of the EU

Tutkielman aiheena on EU:n kilpailuoikeudellinen lähestymistapa challenge-lausekkeisiin teknologinsiirtosopimuksia koskevassa ryhmäpoikkeusasetuksessa. Teknologian lisensoinnin katsotaan olevan tärkeä väline teknologian kehityksen levittämisessä ja innovaation edistämisessä. Joissakin tapauksissa lisenssisopimus voi sisältää kilpailua rajoittavia lausekkeita, joiden voidaan kuitenkin nähdä hyödyttävän kilpailua kokonaisuutta arvostellen. Tällaisia lausekkeita ovat niin sanotut ”no-challenge” – lauseke, eli sopimusehto, jonka nojalla lisenssinsaaja sitoutuu olemaan haastamatta lisensoidun immateriaalioikeuden pätevyyttä ja ”termination-on-challenge” – lauseke, joka antaa lisensoijalle haastettaessa oikeuden päättää lisenssisopimus. Tutkielmassa perehdytään challenge -lausekkeiden hyväksyttävyyden arviointiin Euroopan unionin kilpailuoikeuden näkökulmasta uuden 1.5.2014 voimaan tulleen ryhmäpoikkeusasetuksen valossa. Muissa kuin yksinoikeuksia luovissa teknologiansiirtosopimuksissa olevat termination-on-challenge – lausekkeita tulee uusimmassa ryhmäpoikkeusetuksessa aina perustua yritysten itse suorittamaan tapauskohtaiseen arviointiin. No-challenge – lausekkeet ovat jatkossakin aiemman käytännön mukaisesti ryhmäpoikkeuksen soveltamisalan ulkopuolella. Komission on perustellut challenge - lausekkeiden jättämistä asetuksen ulkopuolelle julkisella intressillä, joka on päästä eroon mitättömistä immateriaalioikeuksista. Komission on katsonut, että challenge – lausekkeiden kilpailua rajoittava ominaisuus on mitättömien immateriaalioikeuksien esiintyminen markkinoilla, mikä osaltaan vääristää kilpailua ja hidastaa toimijoiden markkinoille pääsyä. Toisaalta lausekkeiden voidaan sanoa edistävän kilpailua, sillä ne usein tarjoavat immateriaalioikeuden haltijalle riittävän oikeussuojan ja kannustimen lisensoida teknologia, mikä lisää kilpailua, keksijöiden kannustimia panostaa innovaatioihin sekä vähentää transaktiokustannuksia. Tutkielman keskeinen tulos on ennen kaikkea challenge-lausekkeiden kilpailuvaikutusten tunnistamisessa ja komission perusteluiden kriittisessä arvioinnissa. Komission linjauksen perustelut eivät saa riittävää tukea ottaen huomioon vaikutustenarvioinnin, EU:n tuomioistuinkäytännön sekä taloustieteellisen lähestymistavan. Tutkielman tulosten pohjalta ja tukeutuen eri oikeuslähteisiin, taloustieteellisiin argumentteihin ja oikeusvertailevaan tutkimukseen, on mahdollista tehdä johtopäätöksiä niistä seikoista ja argumenteista, joilla on merkitystä uuden politiikkalinjauksen kilpailuvaikutuksiin.

Torre del Greco distrutta nel 1794 : [vue du site et du Vésuve en éruption] : [peinture]

Collectionneur : Lesouëf, Auguste (1829-1906)

Glenridge Campus Site

Dr. Deeks and Dr. Gibson admiring the Brock Unviersity sign at the Glenrdige Campus. Renovations to the old refigerator factory were only just underway at this time.

Decew Campus Site

Dr. Deeks and Dr. Gibson touring the recently acquired Decew Campus site along a stretch of Merrittville Highway in early 1964. The Sanatorium can be seen in the background.

Decew Campus Site

Dr. Deeks and Dr. Gibson examining the sign at the Decew Campus site along the stretch of Merrittville Highway just north of St. Davids Road. This photo was taken in March of 1964.

Decew Site Tour

Members of Brock University's Founders Committee and the Ontario Advisory Committee on Univesity Affairs tour the Decew site along with Premier John Robarts on June 5, 1963. Premier Robarts had just announced provincial assistance totalling $393,000 for the Brock University project. Pictured here from left to right are Dr. Deeks, Brock University Vice President; Premier Robarts; and James Allan, Provincial Treasurer.

Conformational analysis of antibody binding site using EDMA methods /

Euclidean distance matrix analysis (EDMA) methods are used to distinguish whether or not significant difference exists between conformational samples of antibody complementarity determining region (CDR) loops, isolated LI loop and LI in three-loop assembly (LI, L3 and H3) obtained from Monte Carlo simulation. After the significant difference is detected, the specific inter-Ca distance which contributes to the difference is identified using EDMA.The estimated and improved mean forms of the conformational samples of isolated LI loop and LI loop in three-loop assembly, CDR loops of antibody binding site, are described using EDMA and distance geometry (DGEOM). To the best of our knowledge, it is the first time the EDMA methods are used to analyze conformational samples of molecules obtained from Monte Carlo simulations. Therefore, validations of the EDMA methods using both positive control and negative control tests for the conformational samples of isolated LI loop and LI in three-loop assembly must be done. The EDMA-I bootstrap null hypothesis tests showed false positive results for the comparison of six samples of the isolated LI loop and true positive results for comparison of conformational samples of isolated LI loop and LI in three-loop assembly. The bootstrap confidence interval tests revealed true negative results for comparisons of six samples of the isolated LI loop, and false negative results for the conformational comparisons between isolated LI loop and LI in three-loop assembly. Different conformational sample sizes are further explored by combining the samples of isolated LI loop to increase the sample size, or by clustering the sample using self-organizing map (SOM) to narrow the conformational distribution of the samples being comparedmolecular conformations. However, there is no improvement made for both bootstrap null hypothesis and confidence interval tests. These results show that more work is required before EDMA methods can be used reliably as a method for comparison of samples obtained by Monte Carlo simulations.

A dimensional analysis of the benzylic hydroxylase active site in mortierella isabellina

The spatial limits of the active site in the benzylic hydroxylase enzyme of the fungus Mortierella isabellina were investigated. Several molecular probes were used in incubation experiments to determine the acceptability of each compound by this enzyme. The yields of benzylic alcohols provided information on the acceptability of the particular compound into the active site, and the enantiomeric excess values provided information on the "fit" of acceptable substrates. Measurements of the molecular models were made using Cambridge Scientific Computing Inc. CSC Chem 3D Plus modeling program. i The dimensional limits of the aromatic binding pocket of the benzylic hydroxylase were tested using suitably substituted ethyl benzenes. Both the depth (para substituted substrates) and width (ortho and meta substituted substrates) of this region were investigated, with results demonstrating absolute spatial limits in both directions in the plane of the aromatic ring of 7.3 Angstroms for the depth and 7.1 Angstroms for the width. A minimum requirement for the height of this region has also been established at 6.2 Angstroms. The region containing the active oxygen species was also investigated, using a series of alkylphenylmethanes and fused ring systems in indan, 1,2,3,4-tetrahydronaphthalene and benzocycloheptene substrates. A maximum distance of 6.9 Angstroms (including the 1.5 Angstroms from the phenyl substituent to the active center of the heme prosthetic group of the enzyme) has been established extending directly in ii front of the aromatic binding pocket. The other dimensions in this region of the benzylic hydroxylase active site will require further investigation to establish maximum allowable values. An explanation of the stereochemical distributions in the obtained products has also been put forth that correlates well with the experimental observations.