The complementation of yeast with human or Plasmodium falciparum Hsp90 confers differential inhibitor sensitivities

Developing novel drugs against the unicellular parasite Plasmodium is complicated by the paucity of simple screening systems. Heat-shock proteins are an essential class of proteins for the parasite's cyclical life style between different cellular milieus and temperatures. The molecular chaperone Hsp90 assists a large variety of proteins, but its supporting functions for many proteins that are important for cancer have made it into a well-studied drug target. With a better understanding of the differences between Hsp90 of the malarial parasite and Hsp90 of its human host, new therapeutic options might become available. We have generated a set of isogenic strains of the budding yeast Saccharomyces cerevisiae where the essential yeast Hsp90 proteins have been replaced with either of the two human cytosolic isoforms Hsp90 alpha or Hsp90 beta, or with Hsp90 from Plasmodium falciparum (Pf). All strains express large amounts of the Flag-tagged Hsp90 proteins and are viable. Even though the strain with Pf Hsp90 grows more poorly, it provides a tool to reconstitute additional aspects of the parasite Hsp90 complex and its interactions with substrates in yeast as a living test tube. Upon exposure of the set of Hsp90 test strains to the two Hsp90 inhibitors radicicol (Rd) and geldanamycin (GA), we found that the strain with Pf Hsp90 is relatively more sensitive to GA than to Rd compared to the strains with human Hsp90's. This indicates that this set of yeast strains could be used to screen for new Pf Hsp90 inhibitors with a wider therapeutic window.

Reduction in arterial wall strain with aggressive lipid-lowering therapy in patients with carotid artery disease

Background: Inflammation and biomechanical factors have been associated with the development of vulnerable atherosclerotic plaques. Lipid-lowering therapy has been shown to be effective in stabilizing them by reducing plaque inflammation. Its effect on arterial wall strain, however, remains unknown. The aim of the present study was to investigate the role of high- and low-dose lipid-lowering therapy using an HMG-CoA reductase inhibitor, atorvastatin, on arterial wall strain. Methods and Results: Forty patients with carotid stenosis >40% were successfully followed up during the Atorvastatin Therapy: Effects on Reduction Of Macrophage Activity (ATHEROMA; ISRCTN64894118) Trial. All patients had plaque inflammation as shown by intraplaque accumulation of ultrasmall super paramagnetic particles of iron oxide on magnetic resonance imaging at baseline. Structural analysis was performed and change of strain was compared between high- and low-dose statin at 0 and 12 weeks. There was no significant difference in strain between the 2 groups at baseline (P=0.6). At 12 weeks, the maximum strain was significantly lower in the 80-mg group than in the 10-mg group (0.085±0.033 vs. 0.169±0.084; P=0.001). A significant reduction (26%) of maximum strain was observed in the 80-mg group at 12 weeks (0.018±0.02; P=0.01). Conclusions: Aggressive lipid-lowering therapy is associated with a significant reduction in arterial wall strain. The reduction in biomechanical strain may be associated with reductions in plaque inflammatory burden.

The bentiromide test using plasma p-aminobenzoic acid for diagnosing pancreatic insufficiency in young children. The effect of two different doses and a liquid meal

The bentiromide test was evaluated using plasma p-aminobenzoic acid as an indirect test of pancreatic insufficiency in young children between 2 months and 4 years of age. To determine the optimal test method, the following were examined: (a) the best dose of bentiromide (15 mg/kg or 30 mg/kg); (b) the optimal sampling time for plasma p-aminobenzoic acid, and; (c) the effect of coadministration of a liquid meal. Sixty-nine children (1.6 ± 1.0 years) were studied, including 34 controls with normal fat absorption and 35 patients (34 with cystic fibrosis) with fat maldigestion due to pancreatic insufficiency. Control and pancreatic insufficient subjects were studied in three age-matched groups: (a) low-dose bentiromide (15 mg/kg) with clear fluids; (b) high-dose bentiromide (30 mg/kg) with clear fluids, and; (c) high-dose bentiromide with a liquid meal. Plasma p-aminobenzoic acid was determined at 0, 30, 60, and 90 minutes then hourly for 6 hours. The dose effect of bentiromide with clear liquids was evaluated. High-dose bentiromide best discriminated control and pancreatic insufficient subjects, due to a higher peak plasma p-aminobenzoic acid level in controls, but poor sensitivity and specificity remained. High-dose bentiromide with a liquid meal produced a delayed increase in plasma p-aminobenzoic acid in the control subjects probably caused by retarded gastric emptying. However, in the pancreatic insufficient subjects, use of a liquid meal resulted in significantly lower plasma p-aminobenzoic acid levels at all time points; plasma p-aminobenzoic acid at 2 and 3 hours completely discriminated between control and pancreatic insufficient patients. Evaluation of the data by area under the time-concentration curve failed to improve test results. In conclusion, the bentiromide test is a simple, clinically useful means of detecting pancreatic insufficiency in young children, but a higher dose administered with a liquid meal is recommended.

Roomalaista oikeutta kreikaksi 500-luvun Palestiinassa : Eräitä lakitermejä papyruksessa P. Petra inv. 83

Tutkimuksen tarkoituksena on analysoida eräitä lakitermejä, jotka esiintyvät papyruksessa P. Petra inv. 83. Kyseinen dokumentti, joka sisältää sopimuksen kahden naapuruksen välisen kiistan lopettamiseksi, ajoittuu todennäköisesti vuodelle 574 jKr. ja se kuuluu Jordanian Petrasta vuonna 1993 löydettyyn hiiltyneeseen papyrusarkistoon. Papyrus on tällä hetkellä vielä julkaisematon, ja tämä työ on osa siihen liittyvää perustutkimusta, jonka tarkoituksena on toisaalta selittää tekstin itsensä sisältö, toisaalta arvioida sen antaman informaation merkitystä laajemmassa historiallisessa kontekstissa. Papyrus on kirjoitettu kreikaksi, Bysantin eli Itä-Rooman valtakunnan virallisella kielellä, mutta itse lakitermeistä suurin osa liittyy alun perin latinan kielellä luotuun roomalaiseen oikeuteen. Paikallinen väestö puolestaan oli seemiläistä alkuperää, jolla ei ainoastaan ollut oma kieli, vaan jolla oli ollut ennen valtakuntaan liittämistä omat oikeustraditionsakin. Niinpä papyruksessa esiintyvien termien tutkimuksen kautta nousevat esille monenlaiset laajemmatkin kysymyksenasettelut. Lakitermejä analysoidaan pääasiassa kolmesta näkökulmasta. Ensisijaisena pyrkimyksenä on selvittää niiden tarkka merkitys asiayhteydessään, joka papyruksen fragmentaarisuuden vuoksi ei ole etukäteen selvä, ja siten edistää tekstissä puheena olevien asianhaarojen ymmärtämistä. Toiseksi termien käyttöä koskevat tulokset suhteutetaan yleiseen oikeushistoriaan ja pyritään arvioimaan niiden merkitystä Petrassa käytössä olleen oikeusjärjestelmän kannalta. Kolmas näkökulma on kielitieteellinen, sillä termien käyttö papyruksessa on nähtävä osana laajempaa kehitystä, jossa roomalaisen oikeuden vähittäinen muuttuminen bysanttilaiseksi johti kielten vaihtumiseen ja koko juridisen käsitteistön siirtymiseen latinasta kreikkaan. Siksi tässä työssä käytetään itse papyruksen analyysin lisäksi laajaa vertailumateriaalia, joka koostuu ennen kaikkea roomalaisesta ja bysanttilaisesta lakikirjallisuudesta sekä dokumentaarisesta lähdeaineistosta, etenkin egyptiläisistä papyruksista. Niin tässä papyruksessa kuin muissakin kreikankielisissä lähteissä esiintyvät roomalaiseen oikeuteen liittyvät termit voidaan jaotella suoriin lainoihin, käännöslainoihin sekä komparaatiolainoihin. Jälkimmäisillä tarkoitetaan kreikan kielessä jo aiemmin käytössä olleita termejä, jotka eivät sananmukaiselta merkitykseltään vastaa latinalaisia, mutta joita alettiin käyttää jonkin latinalaisen termin vastineina. Tutkimus tekee selväksi, että olipa kyse mistä lainakategoriasta tahansa, lakitermien siirtyessä kielestä toiseen tapahtui yleensä semanttisia muutoksia eikä termejä aina käytetty samalla tavalla kuin alkukielessä. Merkityskenttä saattoi esimerkiksi supistua taikka laajentua tai sanalle saattoi kehittyä lainautumisen jälkeen täysin uusiakin merkityksiä. Oikeushistorian suhteen on huomioitava ero virallisten säännösten ja provinsseissa noudatettujen käytäntöjen välillä. Kaiken kaikkaan Petra näyttää kuitenkin olleen kiinteä osa Bysantin valtakuntaa, jonka lakeja ainakin pääpiirteissään noudatettiin. Kaikkien termien käytötavat eivät tosin ole johdettavissa suoraan virallisiin lakikorpuksiin, mutta ne eivät myöskään sodi niitä vastaan. Roomalaisen oikeuden tuntemus näyttää olleen Petrassa jopa parempaa kuin esimerkiksi Egyptissä. Mitä tulee papyruksessa puheena oleviin konkreettisiin asianhaaroihin, termien merkityksen ymmärtäminen selventää joidenkin aspektien pääpiirteitä, kun taas yksityskohdat jäävät tekstin fragmentaarisuuden takia useimmiten epäselviksi. Avainsanat: papyrologia, Petra, roomalainen oikeus, terminologia, kreikan kieli, latinan kieli, lainasanat

Low temperature fluorination of sulphur compounds with elemental fluorine

Low temperature fluorination technique is adopted for fluorination of the following sulphur compounds in freon-11 medium (1) Sulphur dioxide (2) Thionyl chloride (3) Sulphuryl chloride (4) Tetrasulphur tetra nitride and (5) Sulphur bromide. All the compounds undergo oxidative fluorination to give rise to sulphur-fluorine compounds except sulphuryl chloride which resists fluorination. Sulphuryl chloride thus behaves as a good solvent medium for fluorination of other reactive compounds like elemental sulphur. Details of the experimental procedures adopted and the identification of the products will be presented.

Electron Mean Energy, Secondary Ionization Coefficients And (E/P)Crit In Binary-Mixtures Of Sf6-N2 And Ccl2f2-N2

Measurements of the ratio of diffusion coefficient to mobility (D/ mu ) of electrons in SF6-N2 and CCl2F2-N2 mixtures over the range 80

Chromosome complements in the spermatogenesis of two penaeid prawns, Penaeus merguiensis and P. esculentus.

Although the fisheries for, and mariculture of, penaeid prawns are of major commercial importance, there has been relatively little research undertaken on the chromosome number, structure and composition in the Penaeidae. One reason for this is due to the relatively small size and large number of chromosomes, which makes production of histological material difficult. In this paper, we report a simple and effective technique for determining chromosome complements during spermatogenesis in two species of penaeid prawns, Penaeus merguiensis and P. esculentus in Australia. The first estimates of the number of chromosomes in these species are given.

Estimating the efficiency of a small beam trawl for sampling tiger prawns Penaeus esculentus and P. semisulcatus in seagrass by removal experiments

The efficiency with which a small beam trawl (1 x 0.5 m mouth) sampled postlarvae and juveniles of tiger prawns Penaeus esculentus and P, semisulcatus at night was estimated in 3 tropical seagrass communities (dominated by Thalassia hemprichii, Syringodium isoetifolium and Enhalus acoroides, respectively) in the shallow waters of the Gulf of Carpentaria in northern Australia. An area of seagrass (40 x 3 m) was enclosed by a net and the beam trawl was repeatedly hand-hauled over the substrate. Net efficiency (q) was calculated using 4 methods: the unweighted Leslie, weighted Leslie, DeLury and Maximum-likelihood (ML) methods. The Maximum-likelihood is the preferred method for estimating efficiency because it makes the fewest assumptions and is not affected by zero catches. The major difference in net efficiencies was between postlarvae (mean ML q +/- 95% confidence limits = 0.66 +/- 0.16) and juveniles of both species (mean q for juveniles in water less than or equal to 1.0 m deep = 0.47 +/- 0.05), i.e. the beam trawl was more efficient at capturing postlarvae than juveniles. There was little difference in net efficiency for P, esculentus between seagrass types (T, hemprichii versus S. isoetifolium), even though the biomass and morphologies of seagrass in these communities differed greatly (biomasses were 54 and 204 g m(-2), respectively). The efficiency of the net appeared to be the same for juveniles of the 2 species in shallow water, but was lower for juvenile P, semisulcatus at high tide when the water was deeper (1.6 to 1.9 m) (0.35 +/- 0.08). The lower efficiency near the time of high tide is possibly because the prawns are more active at high than low tide, and can also escape above the net. Factors affecting net efficiency and alternative methods of estimating net efficiency are discussed.

Ultraviolet bands of mercury bromide

The ultraviolet bands of mercury bromide have been excited in uncondensed discharge and photographed with a quartz Littrow spectrograph. The class II system, lying between\lambda 2900 å to 2700 å, suggested byWieland as due to the triatomic molecule, has been studied in detail and ascribed to the diatomic molecule. The bands in the regionlambda 2900 å to 2770å have been analysed into two systems which may form the two components of a2 II –2 \sigma electronic transition with a2 II interval equal to 969·4 cm–1.Another system most probably due to2 \sigma–2 \sigma has been observed in the region\lambda 2770 to 2720.

Pig effluent-P application can increase risk of P transport: two case studies

Land application of piggery effluent (containing urine, faeces, water, and wasted feed) is under close scrutiny as a potential source of water resource contamination with phosphorus (P). This paper investigates two case studies of the impact of long-term piggery effluent-P application to soil. A Natrustalf (Sodosol) at P1 has received a net load of 3700 kg effluent P/ha over 19 years. The Haplustalf (Dermosol) selected (P2) has received a net load of 310 000 kg P/ha over 30 years. Total, bicarbonate extractable, and soluble P forms were determined throughout the soil profiles for paired (irrigated and unirrigated) sites at P1 and P2, as well as P sorption and desorption characteristics. Surface bicarbonate (PB, 0 - 0.05 m depth) and dilute CaCl2 extractable molybdate-reactive P (PC) have been significantly elevated by effluent irrigation (P1: PB unirrigated 23±1, irrigated 290±6; PC unirrigated 0.03±0.00, irrigated 23.9±0.2. P2: PB unirrigated 72±48, irrigated 3950±1960; PC unirrigated 0.7±0.0, irrigated 443±287 mg P/kg; mean±s.d.). Phosphorus enrichment to 1.5 m, detected as PB, was observed at P2. Elevated concentrations of CaCl2 extractable organic P forms (POC; estimated by non-molybdate reactive P in centrifuged supernatants) were observed from the soil surface of P1 to a depth of 0.4 m. Despite the extent of effluent application at both of these sites, only P1 displayed evidence of significant accumulation of POC. The increase in surface soil total P (0 - 0.05 m depth) due to effluent irrigation was much greater than laboratory P sorption (>25 times for P1; >57 times for P2) for a comparable range of final solution concentrations (desorption extracts ranged from 1-5 mg P/L for P1 and 50-80 mg P/L for P2). Precipitation of sparingly soluble P phases was evidenced in the soils of the P2 effluent application area.

An overview of land application of pig effluent-P using soil P chemistry and mass balance calculations.

Attention is directed at land application of piggery effluent (containing urine, faeces, water, and wasted feed) as a potential source of water resource contamination with phosphorus (P). This paper summarises P-related properties of soil from 0-0.05 m depth at 11 piggery effluent application sites, in order to explore the impact that effluent application has had on the potential for run-off transport of P. The sites investigated were situated on Alfisol, Mollisol, Vertisol, and Spodosol soils in areas that received effluent for 1.5-30 years (estimated effluent-P applications of 100-310000 kg P/ha in total). Total (PT), bicarbonate extractable (PB), and soluble P forms were determined for the soil (0-0.05 m) at paired effluent and no-effluent sites, as well as texture, oxalate-extractable Fe and Al, organic carbon, and pH. All forms of soil P at 0-0.05 m depth increased with effluent application (PB at effluent sites was 1.7-15 times that at no-effluent sites) at 10 of the 11 sites. Increases in PB were strongly related to net P applications (regression analysis of log values for 7 sites with complete data sets: 82.6 % of variance accounted for, p <0.01). Effluent irrigation tended to increase the proportion of soil PT in dilute CaCl2-extractable forms (PTC: effluent average 2.0 %; no-effluent average 0.6%). The proportion of PTC in non-molybdate reactive forms (centrifuged supernatant) decreased (no-effluent average, 46.4 %; effluent average, 13.7 %). Anaerobic lagoon effluent did not reliably acidify soil, since no consistent relationship was observed for pH with effluent application. Soil organic carbon was increased in most of the effluent areas relative to the no-effluent areas. The four effluent areas where organic carbon was reduced had undergone intensive cultivation and cropping. Current effluent management at many of the piggeries failed to maximise the potential for waste P recapture. Ten of the case-study effluent application areas have received effluent-P in excess of crop uptake. While this may not represent a significant risk of leaching where sorption retains P, it has increased the risk of transport of P by run-off. Where such sites are close to surface water, run-off P loads should be managed.

Spool valve mechanism used in a 20 K Gifford-McMahon cycle cryorefrigerator and its effect on the P-V diagram

The design and fabrication of a spool valve for a two-stage Gifford-McMahon cycle cryorefrigerator is described. The effect of this valve on the P-V diagram and practical methods of reducing the P-V degradation are also discussed.

Fast Iterative Division of p-adic Numbers

A fast iterative scheme based on the Newton method is described for finding the reciprocal of a finite segment p-adic numbers (Hensel code). The rate of generation of the reciprocal digits per step can be made quadratic or higher order by a proper choice of the starting value and the iterating function. The extension of this method to find the inverse transform of the Hensel code of a rational polynomial over a finite field is also indicated.

First records of the papaya strain of Papaya ringspot virus (PRSV-P) in French Polynesia and the Cook Islands

The papaya strain of Papaya ringspot virus (PRSV-P), the cause of papaya ringspot disease, was confirmed in French Polynesia and the Cook Islands by double antibody sandwich enzyme linked immunosorbent assay (DAS-ELISA). In French Polynesia, the virus has probably been on the islands of Tahiti and Moorea for several years, but appears not to have spread to eight other islands. In contrast, PRSV-P has only recently appeared in the Cook Islands and is now the subject of an eradication campaign.