Fast quantification of ten psychotropic drugs and metabolites in human plasma by ultra-high performance liquid chromatography tandem mass spectrometry for therapeutic drug monitoring.

A sensitive and selective ultra-high performance liquid chromatography (UHPLC) tandem mass spectrometry (MS/MS) method was developed for the fast quantification of ten psychotropic drugs and metabolites in human plasma for the needs of our laboratory (amisulpride, asenapine, desmethyl-mirtazapine, iloperidone, mirtazapine, norquetiapine, olanzapine, paliperidone, quetiapine and risperidone). Stable isotope-labeled internal standards were used for all analytes, to compensate for the global method variability, including extraction and ionization variations. Sample preparation was performed by generic protein precipitation with acetonitrile. Chromatographic separation was achieved in less than 3.0min on an Acquity UPLC BEH Shield RP18 column (2.1mm×50mm; 1.7μm), using a gradient elution of 10mM ammonium formate buffer pH 3.0 and acetonitrile at a flow rate of 0.4ml/min. The compounds were quantified on a tandem quadrupole mass spectrometer operating in positive electrospray ionization mode, using multiple reaction monitoring. The method was fully validated according to the latest recommendations of international guidelines. Eight point calibration curves were used to cover a large concentration range 0.5-200ng/ml for asenapine, desmethyl-mirtazapine, iloperidone, mirtazapine, olanzapine, paliperidone and risperidone, and 1-1500ng/ml for amisulpride, norquetiapine and quetiapine. Good quantitative performances were achieved in terms of trueness (93.1-111.2%), repeatability (1.3-8.6%) and intermediate precision (1.8-11.5%). Internal standard-normalized matrix effects ranged between 95 and 105%, with a variability never exceeding 6%. The accuracy profiles (total error) were included in the acceptance limits of ±30% for biological samples. This method is therefore suitable for both therapeutic drug monitoring and pharmacokinetic studies.

Dynamic impacts of the inhibition of the molecular chaperone hsp90 on the T-cell proteome have implications for anti-cancer therapy.

The molecular chaperone Hsp90-dependent proteome represents a complex protein network of critical biological and medical relevance. Known to associate with proteins with a broad variety of functions termed clients, Hsp90 maintains key essential and oncogenic signalling pathways. Consequently, Hsp90 inhibitors are being tested as anti-cancer drugs. Using an integrated systematic approach to analyse the effects of Hsp90 inhibition in T-cells, we quantified differential changes in the Hsp90-dependent proteome, Hsp90 interactome, and a selection of the transcriptome. Kinetic behaviours in the Hsp90-dependent proteome were assessed using a novel pulse-chase strategy (Fierro-Monti et al., accompanying article), detecting effects on both protein stability and synthesis. Global and specific dynamic impacts, including proteostatic responses, are due to direct inhibition of Hsp90 as well as indirect effects. As a result, a decrease was detected in most proteins that changed their levels, including known Hsp90 clients. Most likely, consequences of the role of Hsp90 in gene expression determined a global reduction in net de novo protein synthesis. This decrease appeared to be greater in magnitude than a concomitantly observed global increase in protein decay rates. Several novel putative Hsp90 clients were validated, and interestingly, protein families with critical functions, particularly the Hsp90 family and cofactors themselves as well as protein kinases, displayed strongly increased decay rates due to Hsp90 inhibitor treatment. Remarkably, an upsurge in survival pathways, involving molecular chaperones and several oncoproteins, and decreased levels of some tumour suppressors, have implications for anti-cancer therapy with Hsp90 inhibitors. The diversity of global effects may represent a paradigm of mechanisms that are operating to shield cells from proteotoxic stress, by promoting pro-survival and anti-proliferative functions. Data are available via ProteomeXchange with identifier PXD000537.

A composite stratigraphy for the Neoproterozoic Huqf Supergroup of Oman: integrating new litho-, chemo- and chronostratigraphic data of the Mirbat area, southern Oman

The Huqf Supergroup in Oman contains an exceptionally well-preserved and complete sedimentary record of the Middle to Late Neoproterozoic Era. Outcrops of the Huqf Supergroup in northern and central Oman are now well documented, but their correlation with a key succession in the Mirbat area of southern Oman, containing a sedimentary record of two Neoproterozoic glaciations, is poorly understood. Integration of lithostratigraphic, chemostratigraphic and new U-Pb detrital zircon data suggests that the Mirbat Group is best placed within the Cryogenian (c. 850-635 Ma) part of the Huqf Supergroup. The c. I km thick marine deposits of the Arkahawl and Marsham Formations of the Mirbat Group are thought to represent a stratigraphic interval between older Cryogenian and younger Cryogenian glaciations that is not preserved elsewhere in Oman. The bulk of detrital zircons in the Huqf Supergroup originate from Neoproterozoic parent rocks. However, older Mesoproterozoic, Palaeoproterozoic and even Archaean zircons can be recognized in the detrital population from the upper Mahara Group (Fiq Formation) and Nafun Group, suggesting the tapping of exotic sources, probably from the Arabian-Nubian Shield.

Development of MASH TL-3 Transition Between Guardrail and Portable Concrete Barriers, TPF-5(081), 2014

Often, road construction causes the need to create a work zone. In these scenarios, portable concrete barriers (PCBs) are typically installed to shield workers and equipment from errant vehicles as well as prevent motorists from striking other roadside hazards. For an existing W-beam guardrail system installed adjacent to the roadway and near the work zone, guardrail sections are removed in order to place the portable concrete barrier system. The focus of this research study was to develop a proper stiffness transition between W-beam guardrail and portable concrete barrier systems. This research effort was accomplished through development and refinement of design concepts using computer simulation with LS-DYNA. Several design concepts were simulated, and design metrics were used to evaluate and refine each concept. These concepts were then analyzed and ranked based on feasibility, likelihood of success, and ease of installation. The rankings were presented to the Technical Advisory Committee (TAC) for selection of a preferred design alternative. Next, a Critical Impact Point (CIP) study was conducted, while additional analyses were performed to determine the critical attachment location and a reduced installation length for the portable concrete barriers. Finally, an additional simulation effort was conducted in order to evaluate the safety performance of the transition system under reverse-direction impact scenarios as well as to select the CIP. Recommendations were also provided for conducting a Phase II study and evaluating the nested Midwest Guardrail System (MGS) configuration using three Test Level 3 (TL-3) full-scale crash tests according to the criteria provided in the Manual for Assessing Safety Hardware, as published by the American Association of Safety Highway and Transportation Officials (AASHTO).

Disseny d'un sistema de control del consum d'aigua automàtic

Avui en dia s’ha convertit en una necessitat tenir cura del medi ambient i optimitzar els recursos naturals. En el camp per estalviar energia s’han fet grans progressos i disposem d’un gran ventall de dispositius que ens ajuden i ens faciliten l’optimització del consum d’energia. Però és una realitat que en l’estalvi del consum d’aigua el progrés ha estat molt menor i es limita molt a donar consells i repartir dosificadors d’aigua. Qui no ha vist carrers o jardins o cases inundades amb milers de litres d’aigua? Aquesta realitat m’ha portat a dissenyar i desenvolupar un prototip que em permeti tenir un millor control del consum d’aigua. El prototip, a trets principals, consta d’un sensor, una electrovàlvula i una placa Arduino Atmega. El sensor ens permet mesurar els litres consumits durant un cert període de temps. Passat aquest temps de mostreig es compara els litres consumits amb el consum habitual, en aquell període de temps. En cas de sobrepassar el volum programat es tancarà l’electrovàlvula de forma automàtica i rebrem un SMS al telèfon. L’activació de l’alarma es pot ajustar que sigui al igualar-se els dos valors, litres programats i litres consumits. També es pot programar el percentatge que cal sobrepassar de litres consumits per activar l’alarma, com el temps de mostreig. El fet de poder programar tots aquests valors ens permet fer un ajust ideal per a la instal·lació que es vol tenir controlada. A més, el prototip es pot utilitzar per enviar a la companyia d’aigua el valor del comptador de forma automàtica. D’aquesta forma la companyia d’aigua també optimitza recursos estalviant-se el desplaçament de personal a la instal·lació per fer la lectura corresponent. El prototip està basat amb un Arduino Atmega que ens permet el processament de les dades programades i capturades pel sensor. També s’ha incorporat una pantalla TFT Touch 2’8”, que permet visualitzar i programar els valors d’una forma molt més intuïtiva. Per enviar els SMS s’utilitza una placa d’Arduino Cel·lular Shield - SM5100B, a la qual només cal afegir una targeta SIM. A priori, el prototip té un elevat cost al fabricar una sola unitat i pot semblar poc útil. Però ens pot estalviar alguna sorpresa en les factures d’aigua si tenim una fuita i no ens n’adonem fins a veure el rebut de la companyia. Si es fabriqués a grans quantitats es podria abaratir el preu i fer-lo encara més engrescador.

Late Cretaceous to Eocene geology of the South Central American forearc area (southern Costa Rica and western Panama) : initiation and evolution of an intra-oceanic convergent margin

Résumé : L'arc volcanique du sud de l'Amérique Centrale se situe sur la marge SW de la Plaque Caraïbe, au-dessus des plaques subduites de Cocos et Nazca. Il s'agit de l'un des arcs intra-océaniques les plus étudiés au monde, qui est généralement considéré comme s'étant développé à la fin du Crétacé le long d'un plateau océanique (le Plateau Caraïbe ou CLIP) et se trouvant actuellement dans un régime de subduction érosive. Au cours des dernières décennies, des efforts particuliers ont été faits pour comprendre les processus liés à la subduction sur la base d'études géophysiques et géochimiques. Au sud du Costa Rica et à l'ouest du Panama, des complexes d'accrétions et structures à la base de l'arc volcanique ont été exposés grâce à la subduction de rides asismiques et de failles transformantes. Des affleurements, situés jusqu'à seulement 15 km de la fosse, offrent une possibilité unique de mieux comprendre quelques uns des processus ayant lieu le long de la zone de subduction. Nous présentons de nouvelles contraintes sur l'origine de ces affleurements en alliant une étude de terrain poussée, de nouvelles données géochimiques, sédimentaires et paléontologiques, ainsi que des observations structurales effectuées en télédétection. Une nouvelle stratigraphie tectonique entre le Campanien et l'Éocène est définie pour la région d'avant-arc située entre la Péninsule d'Osa (Costa Rica) et la Péninsule d'Azuero (Panama). Nos résultats montrent que la partie externe de la marge est composée d'un arrangement complexe de roches ignées et de séquences sédimentaires de recouvrement qui comprennent principalement le socle de l'arc, des roches d'arc primitif, des fragments de monts sous-marins accrétés et des mélanges d'accrétion. Des preuves sont données pour le développement de l'arc volcanique du sud de l'Amérique Centrale sur un plateau océanique. Le début de la subduction le long de la marge SW de la Plaque Caraïbe a eu lieu au Campanien et a généré des roches d'arc primitif caractérisées par des affinités géochimiques particulières, globalement intermédiaires entre des affinités de plateau et d'arc insulaire. L'arc était mature au Maastrichtien et formait un isthme essentiellement continu entre l'Amérique du Nord et l'Amérique du Sud. Ceci a permis la migration de faunes terrestres entre les Amériques et pourrait avoir contribué à la crise fin Crétacé -Tertiaire en réduisant les courants océaniques subéquatoriaux entre le Pacifique et l'Atlantique. Plusieurs unités composées de fragments de monts sous-marins accrétés sont définies. La nature et l'arrangement structural de ces unités définissent de nouvelles contraintes sur les modes d'accrétion des monts sous-marins/îles océaniques et sur l'évolution de la marge depuis la formation de la zone de subduction. Entre la fin du Crétacé et l'Éocène moyen, la marge a enregistré plusieurs épisodes ponctuels d'accrétion de monts sous-marins alternant avec de la subduction érosive. A l'Éocène moyen, un événement tectonique régional pourrait avoir causé un fort couplage entre les plaques supérieure et inférieure, menant à des taux plus important d'accrétion de monts sous-marins. Durant cette période, la situation le long de la marge était très semblable à la situation actuelle et caractérisée par la présence de monts sous-marins subductants et l'absence d'accrétion de sédiments. L'enregistrement géologique montre qu'il n'est pas possible d'attribuer une nature érosive ou accrétionnaire à la marge dans le passé ou -par analogie- aujourd'hui, parce que (1) les processus d'accrétion et érosifs varient fortement spatialement et temporellement et (2) il est impossible d'évaluer la quantité exacte de matériel tectoniquement enlevé à la marge depuis le début de la subduction. Au sud du Costa Rica, certains fragments de monts sous-marins accrétés sont représentatifs d'une interaction entre une ride et un point chaud dans le Pacifique au Crétacé terminal/Paléocène. L'existence de ces fragments de monts sous-marins et la morphologie du fond de l'Océan Pacifique indiquent que la formation de la ride de Cocos-Nazca s'est formée au moins ~40 Ma avant l'âge proposé par les modèles tectoniques actuels. Au Panama, nous avons identifié une île océanique d'âge début Éocène qui a été accrétée à l'Éocène moyen. L'accrétion a eu lieu à très faible profondeur par détachement de l'île dans la fosse, et a mené à une exceptionnelle préservation des structures volcaniques. Des affleurement comprenant aussi bien des parties basses et hautes de l'édifice volcanique on été étudiées, depuis la phase sous-marine bouclier jusqu'à la phase subaérienne post-bouclier. La stratigraphie nous a permis de différencier les laves de la phase sous-marine de celles de la phase subaérienne. La composition des laves indique une diminution progressive de l'intensité de la fusion partielle de la source et une diminution de la température des laves produites durant les derniers stades de l'activité volcanique. Nous interprétons ces changements comme étant liés à l'éloignement progressif de l'île océanique de la zone de fusion ou point chaud. Abstract The southern Central American volcanic front lies on the SW edge of the Caribbean Plate, inboard of the subducting Cocos and Nazca Plates. It is one of the most studied intra-oceanic convergent margins around the world, which is generally interpreted to have developed in the late Cretaceous along an oceanic plateau (the Caribbean Large Igneous Province or CLIP) and to be currently undergoing a regime of subduction erosion. In the last decades a particular effort has been made to understand subduction-related processes on the basis of geophysical and geochemical studies. In southern Costa Rica and western Panama accretionary complexes and structures at the base of the volcanic front have been exposed in response to subduction of aseismic ridges and transforms. Onland exposures are located as close as to 15 km from the trench and provide a unique opportunity to better understand some of the processes occurring along the subduction zone. We provide new constraints on the origins of these exposures by integrating a comprehensive field work, new geochemical, sedimentary and paleontological data, as well as structural observations based on remote imaging. A new Campanian to Eocene tectonostratigraphy is defined for the forearc area located between the Osa Peninsula (Costa Rica) and the Azuero Peninsula (Panama). Our results show that the outer margin is composed of a complicated arrangement of igneous complexes and overlapping sedimentary sequences that essentially comprise an arc basement, primitive island-arc rocks, accreted seamount fragments and accretionary mélanges. Evidences are provided for the development of the southern Central American arc on the top an oceanic plateau. The subduction initiation along the SW edge of the Caribbean Plate occurred in the Campanian and led to formation of primitive island-arc rocks characterized by unusual geochemical affinities broadly intermediate between plateau and arc affinities. The arc was mature in the Maastrichtian and was forming a predominantly continuous landbridge between the North and South Americas. This allowed migration of terrestrial fauna between the Americas and may have contributed to the Cretaceous-Tertiary crisis by limiting trans-equatorial oceanic currents between the Pacific and the Atlantic. Several units composed of accreted seamount fragments are defined. The nature of the units and their structural arrangement provide new constraints on the modes of accretion of seamounts/oceanic islands and on the evolution of the margin since subduction initiation. Between the late Cretaceous and the middle Eocene, the margin recorded several local episodes of seamount accretion alternating with tectonic erosion. In the middle Eocene a regional tectonic event may have triggered strong coupling between the overriding and subducting plates, leading to higher rates of seamount accretion. During this period the situation along the margin was very similar to the present and characterized by subducting seamounts and absence of sediment accretion. The geological record shows that it is not possible to ascribe an overall erosive or accretionary nature to the margin in the past and, by analogy, today, because (1) accretionary and erosive processes exhibit significant lateral and temporal variations and (2) it is impossible to estimate the exact amount of material tectonically eroded from the margin since subduction initiation. In southern Costa Rica, accreted seamount fragments point toward a plume-ridge interaction in the Pacific in the late Cretaceous/Paleocene. This occurrence of accreted seamount fragments and morphology of the Pacific Ocean floor is indicative of the formation of the Cocos-Nazca spreading system at least ~40 Ma prior to the age proposed in current tectonic models. In Panama, we identified a remarkably-well preserved early Eocene oceanic island that accreted in the middle Eocene. The accretion probably occurred at very shallow depth by detachment of the island in the trench and led to an exceptional preservation of the volcanic structures. Exposures of both deep and superficial parts of the volcanic edifice have been studied, from the submarine-shield to subaerial-postshield stages. The stratigraphy allowed us to distinguish lavas produced during the submarine and subaerial stages. The lava compositions likely define a progressive diminution of source melting and a decrease in the temperature of erupted melts in the latest stages of volcanic activity. We interpret these changes to primarily reflect the progressive migration of the oceanic island out of the melting region or hotspot.

Mineralogical alteration of artificial meteorites during atmospheric entry. The STONE-5 experiment

The generic concept of the artificial meteorite experiment STONE is to fix rock samples bearing microorganisms on the heat shield of a recoverable space capsule and to study their modifications during atmospheric re-entry. The STONE-5 experiment was performed mainly to answer astrobiological questions. The rock samples mounted on the heat shield were used (i) as a carrier for microorganisms and (ii) as internal control to verify whether physical conditions during atmospheric re-entry were comparable to those experienced by "real" meteorites. Samples of dolerite (an igneous rock), sandstone (a sedimentary rock), and gneiss impactite from Haughton Crater carrying endolithic cyanobacteria were fixed to the heat shield of the unmanned recoverable capsule FOTON-M2. Holes drilled on the back side of each rock sample were loaded with bacterial and fungal spores and with dried vegetative cryptoendoliths. The front of the gneissic sample was also soaked with cryptoendoliths. <p>The mineralogical differences between pre- and post-flight samples are detailed. Despite intense ablation resulting in deeply eroded samples, all rocks in part survived atmospheric re-entry. Temperatures attained during re-entry were high enough to melt dolerite, silica, and the gneiss impactite sample. The formation of fusion crusts in STONE-5 was a real novelty and strengthens the link with real meteorites. The exposed part of the dolerite is covered by a fusion crust consisting of silicate glass formed from the rock sample with an admixture of holder material (silica). Compositionally, the fusion crust varies from silica-rich areas (undissolved silica fibres of the holder material) to areas whose composition is "basaltic". Likewise, the fusion crust on the exposed gneiss surface was formed from gneiss with an admixture of holder material. The corresponding composition of the fusion crust varies from silica-rich areas to areas with "gneiss" composition (main component potassium-rich feldspar). The sandstone sample was retrieved intact and did not develop a fusion crust. Thermal decomposition of the calcite matrix followed by disintegration and liberation of the silicate grains prevented the formation of a melt.</p> <p>Furthermore, the non-exposed surface of all samples experienced strong thermal alterations. Hot gases released during ablation pervaded the empty space between sample and sample holder leading to intense local heating. The intense heating below the protective sample holder led to surface melting of the dolerite rock and to the formation of calcium-silicate rims on quartz grains in the sandstone sample. (c) 2008 Elsevier Ltd. All rights reserved.</p>

Sensitivity of yellow passion fruit to ultraviolet-B radiation

The objective of this work was to evaluate the effects of UV-B radiation on the vegetative growth and on the gas exchange characteristics of passion fruit plants (Passiflora edulis) grown in greenhouse. The average unweighted UV-B radiation near the apex of the plants was 8 W m-2 for the UV-B treatment (high UV-B), and 0.8 W m-2 for the control plants (low UV-B). Plants were irradiated with UV-B for 7 hours per day, centered on solar noon, during 16 days. High UV-B radiation resulted in lower shoot dry matter accumulation per plant. The content of UV-B absorbing compounds and anthocyanins was increased in the plants exposed to high UV-B radiation, when compared with the control. UV-B radiation did not affect stomatal conductance or transpiration rate, but reduced photosynthesis and instantaneous water-use efficiency, and increased intercellular CO2 concentration. The accumulation of UV-B-absorbing compounds and anthocyanins did not effectively shield plants from supplementary UV-B radiation, since the growth and photosynthetic processes were significantly reduced.

Palaeotectonic and palaeogeographic evolution of the western Tethys and PeriTethyan domain (IGCP Project 369)

Project No. 369 (''Comparative Evolution of PeriTethyan Rift Basins'') of the International Geological Correlation Program produced a new palaeotectonic-palaeo-geographic atlas of the western PeriTethyan domain. The atlas contains more than two hundred new maps and documents grouped in nine regional sets (Iberia, Polish Trough, Eastern European and Scythian Platforms, Moesian Platform, Levant, Arabian Platform,, Northern Africa, NE Africa-NW Arabia, Libya-Pelagian Shelf plus a set of reconstructions for the whole western Tethys. The area, considered in the atlas stretches. from west to east, from the eastern Atlantic shores to the Urals and, from north to south, from the Baltic shield to equatorial Africa; the time span covered extends from the Late. Carboniferous to the Present. The dataset, resulting from an extensive cooperation between industrial and academic sources, is accessible interactively on a CD-ROM (Stampfli et al., 2001a) and includes legend, timetable, short explanatory notes, full references and additional supporting data. This dataset provides information on the development of the Tethyan realm in space and time. In particular, the relation between the Variscan and Cimmerian cycles in the Mediterranean realm is illustrated by numerous palaeogeographic and palaeotectonic maps.

Novel insulated gamma and lentis retroviral vectors towards safer genetic modification of stem cells

In otherwise successful gene therapy trials insertional mutagenesis has resulted in leukemia. The identification of new short synthetic genetic insulator elements (GIE) which would both prevent such activation effects and shield the transgene from silencing, is a main challenge. Previous attempts with e.g. b-globin HS4, have met with poor efficacy and genetic instability. We have investigated potential improvement with two new candidate synthetic GIEs in SIN-gamma and lentiviral vectors. With each constructs two internal promoters have been tested: either the strong Fr- MuLV-U3 or the housekeeping hPGK.We could identify a specific combination of insulator 2 repeats which translates into best functional activity, high titers and boundary effect in both gammaretro and lentivectors. In target cells a dramatic shift of expression is observed with an homogenous profile the level of which strictly depends on the promoter strength. These data remain stable in both HeLa cells over three months and cord blood HSCs for two months, irrespective of the multiplicity of infection (MOI). In comparison, control native and SIN vectors expression levels show heterogeneous, depend on the MOI and prove unstable. We have undertaken genotoxicity assessment in comparing integration patterns ingenuity in human target cells sampled over three months using high-throughput pyro-sequencing. Data will be presented. Further genotoxicity assessment will include in vivo studies. We have established insulated vectors which harbour both boundary and enhancer-blocking effect and show stable in prolonged in vitro culture conditions. Work performed with support of EC-DG research FP6-NoE, CLINIGENE: LSHB-CT-2006-018933

Ash Particle Erosion on Steam Boiler Convective Section

In this study, equations for the calculation of erosion wear caused by ash particles on convective heat exchanger tubes of steam boilers are presented. Anew, three-dimensional test arrangement was used in the testing of the erosion wear of convective heat exchanger tubes of steam boilers. When using the sleeve-method, three different tube materials and three tube constructions could be tested. New results were obtained from the analyses. The main mechanisms of erosionwear phenomena and erosion wear as a function of collision conditions and material properties have been studied. Properties of fossil fuels have also been presented. When burning solid fuels, such as pulverized coal and peat in steam boilers, most of the ash is entrained by the flue gas in the furnace. In bubbling andcirculating fluidized bed boilers, particle concentration in the flue gas is high because of bed material entrained in the flue gas. Hard particles, such as sharp edged quartz crystals, cause erosion wear when colliding on convective heat exchanger tubes and on the rear wall of the steam boiler. The most important ways to reduce erosion wear in steam boilers is to keep the velocity of the flue gas moderate and prevent channelling of the ash flow in a certain part of the cross section of the flue gas channel, especially near the back wall. One can do this by constructing the boiler with the following components. Screen plates can beused to make the velocity and ash flow distributions more even at the cross-section of the channel. Shield plates and plate type constructions in superheaters can also be used. Erosion testing was conducted with three types of tube constructions: a one tube row, an inline tube bank with six tube rows, and a staggered tube bank with six tube rows. Three flow velocities and two particle concentrations were used in the tests, which were carried out at room temperature. Three particle materials were used: quartz, coal ash and peat ash particles. Mass loss, diameter loss and wall thickness loss measurements of the test sleeves were taken. Erosion wear as a function of flow conditions, tube material and tube construction was analyzed by single-variable linear regression analysis. In developing the erosion wear calculation equations, multi-variable linear regression analysis was used. In the staggered tube bank, erosion wear had a maximum value in a tube row 2 and a local maximum in row 5. In rows 3, 4 and 6, the erosion rate was low. On the other hand, in the in-line tube bank the minimum erosion rate occurred in tube row 2 and in further rows the erosion had an increasing value, so that in a six row tube bank, the maximum value occurred in row 6.

Ruostumattoman teräksen TIG-hitsauksen hitsausnopeuden lisääminen

Diplomityön tavoitteena oli ruostumattoman teräksen koneellisen TIG-hitsauksen hitsausnopeuden lisääminen. Työssä tutkittiin suojakaasun koostumuksen vaikutusta hitsausnopeuteen sekä kahta uudehkoa prosessivariaatiota. Tutkitut prosessit olivat TIG-suurtaajuuspulssihitsaus sekä kaksoiskaasu-TIG-hitsaus. Kirjallisessa osassa perehdyttiin TIG-hitsauksen prosessiparametreihin ja -variaatioihin. Kokeellisessa osassa suoritettiin koehitsauksia hitsausnopeuksien selvittämiseksi. Tavoitteena oli tunkeuman kasvattaminen, mikä mahdollistaa hitsausnopeuden noston läpihitsattaessa. Suojakaasuina käytettiin sekä argonpohjaisia että heliumpohjaisia kaasuja, joihin oli lisätty vetyä. Vedyn avulla hitsausnopeus lisääntyi nykykäytäntöä suuremmillakin pitoisuuksilla. Uutena ilmiönä TIG-hitsauksessa havaittiin keyholen eli lävistysreiän syntyminen korkeita vetypitoisuuksia heliumpohjaisessa suojakaasussa käytettäessä. Keyhole oli kuitenkin erittäin epävakaa, joten jatkotutkimuksien tehtäväksi jää selvittää tarkemmin tämän ilmiön vaikutus. Tutkittuihin prosessivariaatioihin todettiin liittyvän useita laiteteknisiä ongelmia. Hitsausnopeuden suhteen tulokset jäivät vaatimattomiksi. Lähinnä keyholen aukaisemisessa ja aukipitämisessä menetelmistä havaittu hyöty antaa selvän aiheen jatkotutkimuksille.

Sähkömoottorin rakenteen analysointi tärisevässä käytössä

Tämän työn tavoitteena oli suunnitella esimerkkirakenne vaikeisiin olosuhteisiin tarkoitetusta sähkömoottorista. Ensisijaisesti tarkasteltavia osia sähkömoottorin rakenteessa olivat roottoriakseli, laakerointi sekä laakerikilvet. Laakeroinnista tarkasteltiin laakerivaurioiden syntymistä, tarvittavaa esijännitysvoimaa sekä jälkivoitelua. Lisäksi momenttiakselista tarkasteltiin sen vääntövärähtelyominaisuuksia sekä rungosta ja laakerikilvistä niiden jännityksiä B5-kiinnitysasennossa, eli laippakiinnityksessä. Työstä pyrittiin tekemään suunnitteluohje vastaavanlaisiin suunnittelutehtäviin. Tämän työn kirjallisessa osassa tarkasteltiin oikosulkumoottorin rakennetta ja laakerointia, josta perehdyttiin erityisesti erilaisiin kuormitustilanteisiin, voiteluun sekä kestoiänlaskentaan. Lisäksi tarkasteltiin roottoridynamiikkaa ja ominaismuotojen laskentaa. Kokonaisen roottorin, sisältäen roottoriakselin, –levypaketin, laakeroinnin ja ylikuormitussuojan, pienimmäksi ominaistaajuudeksi saatiin 62,1 Hz:ä, joka oli kuitenkin lähes kaksinkertainen verrattaessa roottorin käyntinopeuteen (33,3 Hz:ä). On siis varmaa, että roottorin kestoikä ei heikkene sen ominaistaajuuksien aiheuttamasta resonanssista. Pelkän roottoriakselin pienimmäksi ominaistaajuudeksi saatiin 448,0 Hz:ä. Verrattaessa tätä taajuutta roottorin käyntinopeuteen nähtiin, että roottoriakselin ominaistaajuuksien puolesta rakenne oli selvästi alikriittinen. Tarkasteltaessa roottoriakselin vääntövärähtelyn ominaistaajuutta 12,6 Hz:ä nähtiin, että se oli pienempi kuin moottorin pyörimisnopeus. Tämä ei kuitenkaan ollut moottorin kestoiän kannalta vakavaa. Koska todellisista sähkömoottorin käyttöolosuhteista ei ollut tarkkaa tietoa, tutkittiin laakeroinnin kestoikää kahdessa ääriolosuhteessa, joko moottoriin kohdistuva tärinä oli kokoajan suurin mahdollinen tunnettu tai tärinää ei ollut ollenkaan. Todellinen tilanne on jossakin näiden kahden ääriolosuhteen välissä. Oli kuitenkin varmaa, että tarkasteltava rakenne kestää halutun kestoiän eli 10000 tuntia laakeroinnin puolesta. Laakerikilpien ominaistaajuudet olivat korkeita eikä niillä ollut vaikutusta rakenteen kestoikään. Laakerikilpien korkeat ominaistaajuudet johtuivat niiden jäykästä rakenteesta ja suuresta materiaalipaksuudesta. Tarkasteltaessa momenttiakselin vääntövärähtelyn ominaistaajuutta 7,2 Hz:ä nähtiin, että se oli pienempi kuin moottorin pyörimisnopeus. Tämä ei kuitenkaan ollut moottorin kestoiän kannalta vakavaa, jos ominaistaajuus ja sen kerrannaiset ohitettaisiin sähkömoottorin käytössä hetkellisesti eikä moottoria käytettäisi vääntövärähtelyn taajuudella. Tarkasteltaessa B5-asennon jännityksiä nähdään, että ne kasvoivat rungon ja laakerikilven välisissä kiinnitysruuveissa yllättävän suuriksi. Normaalin ruuvin murtoraja on 640 MPa:a, kun jännitys rungon ja laakerikilven välisissä kiinnitysruuveissa oli suurimmillaan 400 MPa:a. Rakenne oli kuitenkin varmalla puolella kestävyyden suhteen, koska keskimääräinen vetojännitys ruuveissa oli noin 200 MPa:a. Ruuvien jännityksiä voidaan pienentää lisäämällä kiinnitys-ruuvien lukumäärää tai kasvattamalla niiden kokoa. Koko moottorin kiinnitysruuveissa jännitys oli vain 4 MPa:a, koska osan kuormituksesta kantoi laakerikilven olakkeet.

TLR3-Mediated CD8+ Dendritic Cell Activation Is Coupled with Establishment of a Cell-Intrinsic Antiviral State.

Because of their unique capacity to cross-present Ags to CD8(+) T cells, mouse lymphoid tissue-resident CD8(+) dendritic cells (DCs) and their migratory counterparts are critical for priming antiviral T cell responses. High expression of the dsRNA sensor TLR3 is a distinctive feature of these cross-presenting DC subsets. TLR3 engagement in CD8(+) DCs promotes cross-presentation and the acquisition of effector functions required for driving antiviral T cell responses. In this study, we performed a comprehensive analysis of the TLR3-induced antiviral program and cell-autonomous immunity in CD8(+) DC lines and primary CD8(+) DCs. We found that TLR3-ligand polyinosinic-polycytidylic acid and human rhinovirus infection induced a potent antiviral protection against Sendai and vesicular stomatitis virus in a TLR3 and type I IFN receptor-dependent manner. Polyinosinic-polycytidylic acid-induced antiviral genes were identified by mass spectrometry-based proteomics and transcriptomics in the CD8(+) DC line. Nanostring nCounter experiments confirmed that these antiviral genes were induced by TLR3 engagement in primary CD8(+) DCs, and indicated that many are secondary TLR3-response genes requiring autocrine IFN-β stimulation. TLR3-activation thus establishes a type I IFN-dependent antiviral program in a DC subtype playing crucial roles in priming adaptive antiviral immune responses. This mechanism is likely to shield the priming of antiviral responses against inhibition or abrogation by the viral infection. It could be particularly relevant for viruses detected mainly by TLR3, which may not trigger type I IFN production by DCs that lack TLR3, such as plasmacytoid DCs or CD8(-) DCs.