Differential pharmacologic properties of the two C75 enantiomers: (+)-C75 is a strong anorectic drug. (-)-C75 has antitumour activity

C75 is a synthetic compound described as having antitumoral properties. It produces hypophagia and weight loss in rodents, limiting its use in cancer therapy but identify- ing it as a potential anti-obesity drug. C75 is a fatty acid synthase (FAS) inhibitor and, through its coenzyme A (CoA) derivative, it acts as a carnitine palmitoyltransferase (CPT) 1 inhibitor. Racemic mixtures of C75 have been used in all the previous studies; however, the potential dif- ferent biological activities of C75 enantiomers have not been examined yet. To address this question we synthesized the two C75 enantiomers separately. Our results showed that ( )- C75 inhibits FAS activity in vitro and has a cytotoxic effect on tumor cell lines, without affecting food consumption. (+)-C75 inhibits CPT1 and its administration produces anorexia, suggesting that central inhibition of CPT1 is essential for the anorectic effect of C75. The differential activity of C75 enantiomers may lead to the development of potential new specific drugs for cancer and obesity.

Minimal requirements for parameters to be used for the development of predictive models for microbial source tracking. The example of the pair somatic coliphages and phages infecting Bacteroides

Several methods and approaches for measuring parameters to determine fecal sources of pollution in water have been developed in recent years. No single microbial or chemical parameter has proved sufficient to determine the source of fecal pollution. Combinations of parameters involving at least one discriminating indicator and one universal fecal indicator offer the most promising solutions for qualitative and quantitative analyses. The universal (nondiscriminating) fecal indicator provides quantitative information regarding the fecal load. The discriminating indicator contributes to the identification of a specific source. The relative values of the parameters derived from both kinds of indicators could provide information regarding the contribution to the total fecal load from each origin. It is also essential that both parameters characteristically persist in the environment for similar periods. Numerical analysis, such as inductive learning methods, could be used to select the most suitable and the lowest number of parameters to develop predictive models. These combinations of parameters provide information on factors affecting the models, such as dilution, specific types of animal source, persistence of microbial tracers, and complex mixtures from different sources. The combined use of the enumeration of somatic coliphages and the enumeration of Bacteroides-phages using different host specific strains (one from humans and another from pigs), both selected using the suggested approach, provides a feasible model for quantitative and qualitative analyses of fecal source identification.

Differential pharmacologic properties of the two C75 enantiomers: (+)-C75 is a strong anorectic drug. (-)-C75 has antitumour activity

C75 is a synthetic compound described as having antitumoral properties. It produces hypophagia and weight loss in rodents, limiting its use in cancer therapy but identify- ing it as a potential anti-obesity drug. C75 is a fatty acid synthase (FAS) inhibitor and, through its coenzyme A (CoA) derivative, it acts as a carnitine palmitoyltransferase (CPT) 1 inhibitor. Racemic mixtures of C75 have been used in all the previous studies; however, the potential dif- ferent biological activities of C75 enantiomers have not been examined yet. To address this question we synthesized the two C75 enantiomers separately. Our results showed that ( )- C75 inhibits FAS activity in vitro and has a cytotoxic effect on tumor cell lines, without affecting food consumption. (+)-C75 inhibits CPT1 and its administration produces anorexia, suggesting that central inhibition of CPT1 is essential for the anorectic effect of C75. The differential activity of C75 enantiomers may lead to the development of potential new specific drugs for cancer and obesity.

The thermal circuits of the Argentera Massif (western Alps, Italy): An example of low-enthalpy geothermal resources controlled by Neogene alpine tectonics

This work presents geochemistry and structural geology data concerning the low enthalpy geothermal circuits of the Argentera crystalline Massif in northwestern Italian Alps. I n this area some thermal springs (50-60 degreesC), located in the small Bagni di Vinadio village, discharge mixtures made up of a Na-Cl end-member and a Na-SO4 component. The latter is also discharged by the thermal springs of Terme di Valdieri located some kilometres apart within the same tectonic complex. Both end-members share the same meteoric origin and the same reservoir temperature, which is close to 150 degreesC. Explanations are thus required to understand how they reach the surface and how waters of the same origin and circulating in similar rocks can attain such different compositions. Sodium-sulphate waters discharged at both sites, likely represent the common interaction product of meteoric waters with the widespread granitic-migmatitic rocks of the Argentera Massif, whereas Na-CI waters originate through leaching of mineralised cataclastic rocks, which are rich in phyllosilicatic minerals and fluid inclusions, both acting as Cl- sources. Due to the relatively low inferred geothermal gradient of the region, -25C/km, meteoric waters have to descend to depths of 5.5-6 km to attain temperatures of similar to 150 degreesC. These relevant depths can be reached by descending meteoric waters, due to the recent extensional stress field, which allows the development of geothermal circulations at greater depths than in other sectors of the Alps by favouring a greater fractures aperture. The ascent of the thermal waters rakes place along brittle shear zones. In both sites, the thermal waters emerge at the bottoms of the valleys, close to either the lateral termination of a brittle shear zone at Terme di Valdieri, or a step-over between two en-echelon brittle shear zones at Bagni di Vinadio. These observations attest to a strong control operated on the location of outlet regions by both brittle tectonics and the minima in hydraulic potential inside the fractured massif.

Production technology for entomopathogenic fungus using a biphasic culture system

The objective of this research was to evaluate combinations of liquid media obtained from agro-industrial residues and by-products, with solid media prepared with mixtures of grains and their derivatives, aiming to increase the production of JAB 02 and JAB 45 isolates of Lecanicillium lecanii. Sporulation, conidial viability and process yield were evaluated as well as the production costs using the JAB 45 isolate as a model system were analyzed. The production of JAB 02 was not increased using the biphasic culture. For JAB 45, some combinations provided an increase in yield, especially cheese whey with wheat bran and wheat grain, with lower production costs. Viability was not influenced by the production method, and the combinations showed no differences in the process yield. The biphasic method is suitable for the production of L. lecanii, and proves to be an appropriate technology to use in mass production by biofactories.

The role of cisplatin and NAMI-A plasma-protein interactions in relation to combination therapy

The aim of the study is to evaluate the differences of protein binding of NAMI-A, a new ruthenium drug endowed with selective antimetastatic properties, and of cisplatin and to ascertain the possibility to use two drugs based on heavy metals in combination to treat solid tumour metastases. For this purpose, we have developed a technique that allows the proteins, to which metal drugs bind, to be identified from real protein mixtures. Following incubation with the drugs, the bands containing platinum and/or ruthenium are separated by native PAGE, SDS-PAGE and 2D gel electrophoresis, and identified using laser ablation inductively coupled plasma mass spectrometry. Both drugs interact with essentially the same proteins which, characterised by proteomics, are human serum albumin precursor, macroglobulin alpha 2 and human serotransferrin precursor. The interactions of NAMI-A are largely reversible whereas cisplatin forms stronger interactions that are less reversible. These data correlate well with the MCa mammary carcinoma model on which full doses of NAMI-A combined with cisplatin show additive effects as compared to each treatment taken alone, independently of whether NAMI-A precedes or follows cisplatin. Furthermore, the implication from this study is that the significantly lower toxicity of NAMI-A, compared to cisplatin, could be a consequence of differences in the mode of binding to plasma proteins, involving weaker interactions compared to cisplatin.

Bituminous Mixes Prepared with Ungraded Local Aggregates, Iowa Highway Research Board Bulletin No. 19, 1960

Joint Publications from Iowa Engineering Experiment Station - Bulletin No. 190 and Iowa Highway Research Board - Bulletin No. 19. This bulletin is a report on the development of bituminous paving mixtures containing various local materials and asphaltic binders. The laboratory investigations described in this bulletin were performed as part of Iowa Highway Research Board project HR-20, "Treating Loess, Fine Sands, and Limestone Dusts With Liquid Binders." This project was awarded to the Iowa Engineering Experiment Station of Iowa State University in 1952, and continued to June, 1958.

Weaker ligands can dominate an odor blend due to syntopic interactions.

Most odors in natural environments are mixtures of several compounds. Perceptually, these can blend into a new "perfume," or some components may dominate as elements of the mixture. In order to understand such mixture interactions, it is necessary to study the events at the olfactory periphery, down to the level of single-odorant receptor cells. Does a strong ligand present at a low concentration outweigh the effect of weak ligands present at high concentrations? We used the fruit fly receptor dOr22a and a banana-like odor mixture as a model system. We show that an intermediate ligand at an intermediate concentration alone elicits the neuron's blend response, despite the presence of both weaker ligands at higher concentration, and of better ligands at lower concentration in the mixture. Because all of these components, when given alone, elicited significant responses, this reveals specific mixture processing already at the periphery. By measuring complete dose-response curves we show that these mixture effects can be fully explained by a model of syntopic interaction at a single-receptor binding site. Our data have important implications for how odor mixtures are processed in general, and what preprocessing occurs before the information reaches the brain.

A Progress Report on Treating Loess, Fine Sands and Soft Limestones with Liquid Binders, HR-20, 1954

Certain areas of Iowa abound in loess, others contain soft limestones that are readily and cheaply available, and a large portion of the state is underlaid with sand. None of these materials is considered suitable in present practices for use in all-weather road construction. The loess is too fine and too difficult to handle; the limestones are considered too soft, and some of the harder ones unsound for this use; the sands are not naturally of the desired gradation and do not lend themselves to blending into satisfactory gradations. The purpose of this project is, therefore, to study and develop means and to determine the feasibility of using these materials, loess, fine sand, and soft limestones, either separately or in combinations in conjunction with liquid binders to produce paving mixtures applicable for all-weather road construction. Also included in the project was the development of methods of processing any of these materials, if necessary, to make them suitable for the desired purpose

The Use of Fly Ash in Highway Construction, HR-1031, Progress Report, 1986

In 1982 the Iowa DOT allowed a successful bidder the option of submitting materials and proportions using fly ash to produce a portland cement concrete (PCC) paving mixture to meet a specified compressive strength. The contractor, Irving F. Jensen, received approval for the use of a concrete mixture utilizing 500 lbs. of portland cement and 88 lbs. of fly ash as a replacement of 88 lbs. of portland cement. The PCC mixture was utilized on the Muscatine County US 61 relocation bypass paved as project F-61-4(32)--20-70. A Class "C" fly ash obtained from the Chillicothe electric generating plant approximately 100 miles away was used in the project. This use of fly ash in lieu of portland cement resulted in a cost savings of $64,500 and an energy savings of approximately 16 billion BTU. The compressive strength of this PCC mixture option was very comparable to concrete mixtures produced without the use of fly ash. The pavement has been performing very well. The substitution of fly ash for 15% of the cement has been allowed as a contractor's option since 1984. Due to the cost savings, it has been used in almost all Iowa PCC paving since that time.

Textural controls on induced polarization and permeability in granular media

The spatial resolution visualized with hydrological models and the conceptualized images of subsurface hydrological processes often exceed resolution of the data collected with classical instrumentation at the field scale. In recent years it was possible to increasingly diminish the inherent gap to information from point like field data through the application of hydrogeophysical methods at field-scale. With regards to all common geophysical exploration techniques, electric and electromagnetic methods have arguably to greatest sensitivity to hydrologically relevant parameters. Of particular interest in this context are induced polarisation (IP) measurements, which essentially constrain the capacity of a probed subsurface region to store an electrical charge. In the absence of metallic conductors the IP- response is largely driven by current conduction along the grain surfaces. This offers the perspective to link such measurements to the characteristics of the solid-fluid-interface and thus, at least in unconsolidated sediments, should allow for first-order estimates of the permeability structure.¦While the IP-effect is well explored through laboratory experiments and in part verified through field data for clay-rich environments, the applicability of IP-based characterizations to clay-poor aquifers is not clear. For example, polarization mechanisms like membrane polarization are not applicable in the rather wide pore-systems of clay free sands, and the direct transposition of Schwarz' theory relating polarization of spheres to the relaxation mechanism of polarized cells to complex natural sediments yields ambiguous results.¦In order to improve our understanding of the structural origins of IP-signals in such environments as well as their correlation with pertinent hydrological parameters, various laboratory measurements have been conducted. We consider saturated quartz samples with a grain size spectrum varying from fine sand to fine gravel, that is grain diameters between 0,09 and 5,6 mm, as well as corresponding pertinent mixtures which can be regarded as proxies for widespread alluvial deposits. The pore space characteristics are altered by changing (i) the grain size spectra, (ii) the degree of compaction, and (iii) the level of sorting. We then examined how these changes affect the SIP response, the hydraulic conductivity, and the specific surface area of the considered samples, while keeping any electrochemical variability during the measurements as small as possible. The results do not follow simple assumptions on relationships to single parameters such as grain size. It was found that the complexity of natural occurring media is not yet sufficiently represented when modelling IP. At the same time simple correlation to permeability was found to be strong and consistent. Hence, adaptations with the aim of better representing the geo-structure of natural porous media were applied to the simplified model space used in Schwarz' IP-effect-theory. The resulting semi- empiric relationship was found to more accurately predict the IP-effect and its relation to the parameters grain size and permeability. If combined with recent findings about the effect of pore fluid electrochemistry together with advanced complex resistivity tomography, these results will allow us to picture diverse aspects of the subsurface with relative certainty. Within the framework of single measurement campaigns, hydrologiste can than collect data with information about the geo-structure and geo-chemistry of the subsurface. However, additional research efforts will be necessary to further improve the understanding of the physical origins of IP-effect and minimize the potential for false interpretations.¦-¦Dans l'étude des processus et caractéristiques hydrologiques des subsurfaces, la résolution spatiale donnée par les modèles hydrologiques dépasse souvent la résolution des données du terrain récoltées avec des méthodes classiques d'hydrologie. Récemment il est possible de réduire de plus en plus cet divergence spatiale entre modèles numériques et données du terrain par l'utilisation de méthodes géophysiques, notamment celles géoélectriques. Parmi les méthodes électriques, la polarisation provoquée (PP) permet de représenter la capacité des roches poreuses et des sols à stocker une charge électrique. En l'absence des métaux dans le sous-sol, cet effet est largement influencé par des caractéristiques de surface des matériaux. En conséquence les mesures PP offrent une information des interfaces entre solides et fluides dans les matériaux poreux que nous pouvons lier à la perméabilité également dirigée par ces mêmes paramètres. L'effet de la polarisation provoquée à été étudié dans différentes études de laboratoire, ainsi que sur le terrain. A cause d'une faible capacité de polarisation des matériaux sableux, comparé aux argiles, leur caractérisation par l'effet-PP reste difficile a interpréter d'une manière cohérente pour les environnements hétérogènes.¦Pour améliorer les connaissances sur l'importance de la structure du sous-sol sableux envers l'effet PP et des paramètres hydrologiques, nous avons fait des mesures de laboratoire variées. En détail, nous avons considéré des échantillons sableux de quartz avec des distributions de taille de grain entre sables fins et graviers fins, en diamètre cela fait entre 0,09 et 5,6 mm. Les caractéristiques de l'espace poreux sont changées en modifiant (i) la distribution de taille des grains, (ii) le degré de compaction, et (iii) le niveau d'hétérogénéité dans la distribution de taille de grains. En suite nous étudions comment ces changements influencent l'effet-PP, la perméabilité et la surface spécifique des échantillons. Les paramètres électrochimiques sont gardés à un minimum pendant les mesures. Les résultats ne montrent pas de relation simple entre les paramètres pétro-physiques comme par exemples la taille des grains. La complexité des media naturels n'est pas encore suffisamment représenté par les modèles des processus PP. Néanmoins, la simple corrélation entre effet PP et perméabilité est fort et consistant. En conséquence la théorie de Schwarz sur l'effet-PP a été adapté de manière semi-empirique pour mieux pouvoir estimer la relation entre les résultats de l'effet-PP et les paramètres taille de graines et perméabilité. Nos résultats concernant l'influence de la texture des matériaux et celles de l'effet de l'électrochimie des fluides dans les pores, permettront de visualiser des divers aspects du sous-sol. Avec des telles mesures géo-électriques, les hydrologues peuvent collectionner des données contenant des informations sur la structure et la chimie des fluides des sous-sols. Néanmoins, plus de recherches sur les origines physiques de l'effet-PP sont nécessaires afin de minimiser le risque potentiel d'une mauvaise interprétation des données.

Hitsaussuojakaasujen tehokas ja taloudellinen käyttö

Suojakaasun päätehtävänä on suojata hitsaustapahtumaa ympäröivän ilman vaikutukselta. Päätehtävän lisäksi suojakaasullavoidaan vaikuttaa suoraan tai välillisesti lähes kaikkiin hitsauksen asioihin, joista laatu, tehokkuus ja taloudellisuus muodostuvat. Suojakaasuja tarvitsevat hitsausmenetelmät ovat: kaasukaarihitsausprosessit (MIG/MAG-, TIG- ja plasmahitsaus), laserhitsaus sekä näiden yhdistelmät eli hybridihitsausmenetelmät sekä MIG-juotto. Hitsaussuojakaasujen peruskaasu tänä päivänä on argon, johon hitsausprosessista tai materiaalistariippuen sekoitetaan hiilidioksidia, heliumia, vetyä tai happea. Pääsääntöisesti hitsaussuojakaasut ovat kahden komponentin kaasuja, mutta 3-komponenttikaasut ovat yleistymässä. Sopivalla suojakaasuseostuksella saadaan erittäin merkittävä hyöty tuottavuuden lisääntyessä ja laadun parantuessa. Suojakaasujen oikealla toimitusmuodolla on merkittävä vaikutus kokonaiskustannuksiin. Uudet, kehittyneet sekoitinlaitteet mahdollistavat tarkat osakomponenttien sekoittamiset hitsauspaikalla. Seokset ovat jatkuvasti analysoitavissa ja jäljitettävissä. Suojakaasujen kierrätys on erityisesti kalliiden kaasujen, kuten helium ja argon, kohdalta tulevaisuuden haaste ja mahdollisuus. Suojakaasulla on suuri merkitys hitsauksen tuottavuuteen, taloudellisuuteen ja myös hitsausympäristöön ja työturvallisuuteen. Robottihitsauksen lisääntyminen asettaa vaatimuksia, joihinoikein valitulla suojakaasulla voidaan myönteisesti vaikuttaa. Tehokashitsaus on valmistusprosessin tärkeä osa, jossa oikein valituilla suojakaasuilla saavutetaan merkittävä tuottavuuden lisäys vaikuttamalla kaariominaisuuksiin, tunkeumaan, roiskeisiin, nopeuteen, hitsimetallurgiaan, lämmöntuontiin ja hitsausympäristöön. Diplomityössä tutkittiin casena Peikko Finland Oy:n suojakaasujärjestelmät, niiden tehokkuus, toimivuus ja sopivuus konepajan tuotantoon ja erityisesti robottihitsaukseen.

Effect of Shielding Gases in Laser Welding of Aluminium Alloys

High reflectivity to laser light, alloying element evaporation during high power laser welding makes aluminium alloys highly susceptibility to weld defects such as porosity, cracking and undercutting. The dynamic behaviour of the keyhole, due to fluctuating plasma above the keyhole and the vaporization ofthe alloying elements with in the keyhole, is the key problem to be solved for the improvement of the weld quality and stabilization of the keyhole dynamics isperhaps the single most important development that can broaden the application of laser welding of aluminium alloys. In laser welding, the shielding gas is commonly used to stabilize the welding process, to improve the welded joint features and to protect the welded seam from oxidation. The chemicalcomposition of the shielding gas is a key factor in achieving the final qualityof the welded joints. Wide range of shielding gases varying from the pure gasesto complex mixtures based on helium, argon, nitrogen and carbon dioxide are commercially available. These gas mixtures should be considered in terms of their suitability during laser welding of aluminium alloys to produce quality welds. The main objective of the present work is to study the effect of the shielding gascomposition during laser welding of aluminium alloys. Aluminium alloy A15754 was welded using 3kW Nd-YAG laser (continuous wave mode). The alloy samples were butt welded with different shielding gases (pure and mixture of gases) so that high quality welds with high joint efficiencies could be produced. It was observed that the chemical composition of the gases influenced the final weld quality and properties. In general, the mixture gases, in correct proportions, enabled better utilisation of the properties of the mixing gases, stabilized the welding process and produced better weld quality compared to the pure shielding gases.

Puukuitulujitteiset muovikomposiitit puunjalostusteollisuudessa

Puukuitulujitteisten muovikomposiittien käyttömäärät ovat maailmanlaajuisesti kasvaneet jatkuvasti viimeisen 15 vuoden aikana.Kasvun on ennustettu jatkuvan voimakkaana myös tulevaisuudessa. Diplomityön tavoitteena oli selvittää puukuitulujitteisten muovikomposiittimateriaalien soveltuvuus erääseen, mahdollisesti rakennusteollisuuden käyttöön tulevaan, tuotteeseen. Tutkittaviksi materiaaliyhdistelmiksi valittiin sekä kerta- että kestomuovin ja puu- jauhon seos. Puujauho oli koivupuista sahaus- ja hiontajätettä. Molemmissa tapauksissa puun osuus komposiitissa oli 30 p-%. Koekappaleiden valmistuksessakäytettiin koivupuisia muotteja, joihin materiaali annosteltiin. Kertamuovin japuujauhon seos kovettui huoneenlämmössä. Kestomuovin ja puujauhon seoksen sulatukseen käytettiin lämmitettävillä puristinlevyillä varustettua aihiopuristinta. Koekappaleille määritettiin taivutuslujuudet taivutuskokeen avulla. Koekappaleiden taivutuslujuuksia verrattiin mm. lattialastulevyn ja koivuliimalevyn arvoihin. Liimalevyn taivutuslujuus muihin verrattuna oli huomattavasti suurempi. Komposiittimateriaalista valmistettujen koekappaleiden taivutuslujuus oli lähellä lattia-lastulevyn tasoa, osittain jonkin verran parempikin. Diplomityössä saatujen tulosten perusteella voidaan todeta puukuitulujitteisilla muovikomposiiteilla olevan kehityspotentiaalia myös tutkimuskohteen tyyppisissä ratkaisuissa. Jatkotutkimusta tulisi kohdistaa ennen kaikkea kestomuovipohjaisen komposiittimateriaalinsuuntaan.

Linjasekoittimensekoituskyvyn määrittäminen

Työn tavoitteena oli kehittää sekoituskyvyn empiirinen monimuuttujafunktio eräälle dynaamiselle linjasekoittimelle. Monimuuttujafunktio oli tarkoitus kehittää sekoittimen kierrosnopeuden, virtaavien materiaalien ja tilavuusvirtausten perus-teella. Työn kirjallisuusosassa tarkasteltiin pääosin dynaamisia linjasekoittimia ja niiden toimintaperiaatteita sekä sekoituskyvyn määrittämiseen soveltuvia mittausmene-telmiä. Sekoitettavien aineiden epähomogeenisuus määritettiin mittaamalla termoelemen-teillä sekoittimen jälkeisen virran lämpötilavaihtelut. Sekoitettavina aineina käy-tettiin kolmea erilaista seosta: vesi-vesi-, kuitususpensio-vesi- ja karboksyylime-tyyliselluloosa-vesiseoksia. Muita muuttujia kokeissa olivat neljä eri sekoittimen kierrosnopeutta, neljä eri päävirran tilavuusvirtausta ja kolme päävirran sekäsii-hen lisättävän sivuvirran suhdetta. Monimuuttujafunktiokehitettiin vain kuitususpensio-vesiajojen pohjalta muilla seoksilla tehtyjen koeajojen osittaisen epäonnistumisen vuoksi. Hallitsevaksi pa-rametriksi monimuuttujafunktiossa osoittautui sekoittimen kierrosnopeus. Osittai-nen epäonnistuminen kokeissa johtui osaksi termoelementtien käytön sopimatto-muudesta sekoituskyvyn määrittämiseen ja osaksi sekoitettavien aineiden valin-nasta. Jatkotutkimuksiaajatellen muista sekoituskyvyn mittaamiseen käytettävissä olevista menetelmistäkäyttökelpoisimmaksi arvioitiin sähkötomografia.