6.2

Airborne particles can come from a variety of sources and contain variable chemical constituents. Some particles are formed by natural processes, such as volcanoes, erosion, sea spray, and forest fires, while other are formed by anthropogenic processes, such as industrial- and motor vehicle-related combustion, road-related wear, and mining. In general, larger particles (those greater than 2.5 μm) are formed by mechanical processes, while those less than 2.5 μm are formed by combustion processes. The chemical composition of particles is highly influenced by the source: for combustion-related particles, factors such as temperature of combustion, fuel type, and presence of oxygen or other gases can also have a large impact on PM composition. These differences can often be observed at a regional level, such as the greater sulphate-composition of PM in regions that burn coal for electricity production (which contains sulphur) versus regions that do not. Most countries maintain air monitoring networks, and studies based on the resulting data are the most common basis for epidemiology studies on the health effects of PM. Data from these monitoring stations can be used to evaluate the relationship between community-level exposure to ambient particles and health outcomes (i.e., morbidity or mortality from various causes). Respiratory and cardiovascular outcomes are the most commonly assessed, although studies have also considered other related specific outcomes such as diabetes and congenital heart disease. The data on particle characteristics is usually not very detailed and most often includes some combination of PM2.5, PM10, sulphate, and NO2. Other descriptors that are less commonly found include particle number (ultrafine particles), metal components of PM, local traffic intensity, and EC/OC. Measures of association are usually reported per 10 μg/m3 or interquartile range increase in pollutant concentration. As the exposure data are taken from regional monitoring stations, the measurements are not representative of an individual's exposure. Particle size is an important descriptor for understanding where in the human respiratory system the particles will deposit: as a general rule, smaller particles penetrate to deeper regions of the lungs. Initial studies on the health effects of particulate matter focused on mass of the particles, including either all particles (often termed total suspended particulate or TSP) or PM10 (all particles with an aerodynamic diameter less than 10 μm). More recently, studies have considered both PM10 and PM2.5, with the latter corresponding more directly to combustion-related processes. UFPs are a dominant source of particles in terms of PNC, yet are negligible in terms of mass. Very few epidemiology studies have measured the effect of UFPs on health; however, the numbers of studies on this topic are increasing. In addition to size, chemical composition is of importance when understanding the toxicity of particles. Some studies consider the composition of particles in addition to mass; however this is not common, in part due the cost and labour involved in such analyses.

Results of An International Study of Quantitative BCR/ABL Assays Using Defined RNA Samples

Molecular monitoring of BCR/ABL transcripts by real time quantitative reverse transcription PCR (qRT-PCR) is an essential technique for clinical management of patients with BCR/ABL-positive CML and ALL. Though quantitative BCR/ABL assays are performed in hundreds of laboratories worldwide, results among these laboratories cannot be reliably compared due to heterogeneity in test methods, data analysis, reporting, and lack of quantitative standards. Recent efforts towards standardization have been limited in scope. Aliquots of RNA were sent to clinical test centers worldwide in order to evaluate methods and reporting for e1a2, b2a2, and b3a2 transcript levels using their own qRT-PCR assays. Total RNA was isolated from tissue culture cells that expressed each of the different BCR/ABL transcripts. Serial log dilutions were prepared, ranging from 100 to 10-5, in RNA isolated from HL60 cells. Laboratories performed 5 independent qRT-PCR reactions for each sample type at each dilution. In addition, 15 qRT-PCR reactions of the 10-3 b3a2 RNA dilution were run to assess reproducibility within and between laboratories. Participants were asked to run the samples following their standard protocols and to report cycle threshold (Ct), quantitative values for BCR/ABL and housekeeping genes, and ratios of BCR/ABL to housekeeping genes for each sample RNA. Thirty-seven (n=37) participants have submitted qRT-PCR results for analysis (36, 37, and 34 labs generated data for b2a2, b3a2, and e1a2, respectively). The limit of detection for this study was defined as the lowest dilution that a Ct value could be detected for all 5 replicates. For b2a2, 15, 16, 4, and 1 lab(s) showed a limit of detection at the 10-5, 10-4, 10-3, and 10-2 dilutions, respectively. For b3a2, 20, 13, and 4 labs showed a limit of detection at the 10-5, 10-4, and 10-3 dilutions, respectively. For e1a2, 10, 21, 2, and 1 lab(s) showed a limit of detection at the 10-5, 10-4, 10-3, and 10-2 dilutions, respectively. Log %BCR/ABL ratio values provided a method for comparing results between the different laboratories for each BCR/ABL dilution series. Linear regression analysis revealed concordance among the majority of participant data over the 10-1 to 10-4 dilutions. The overall slope values showed comparable results among the majority of b2a2 (mean=0.939; median=0.9627; range (0.399 - 1.1872)), b3a2 (mean=0.925; median=0.922; range (0.625 - 1.140)), and e1a2 (mean=0.897; median=0.909; range (0.5174 - 1.138)) laboratory results (Fig. 1-3)). Thirty-four (n=34) out of the 37 laboratories reported Ct values for all 15 replicates and only those with a complete data set were included in the inter-lab calculations. Eleven laboratories either did not report their copy number data or used other reporting units such as nanograms or cell numbers; therefore, only 26 laboratories were included in the overall analysis of copy numbers. The median copy number was 348.4, with a range from 15.6 to 547,000 copies (approximately a 4.5 log difference); the median intra-lab %CV was 19.2% with a range from 4.2% to 82.6%. While our international performance evaluation using serially diluted RNA samples has reinforced the fact that heterogeneity exists among clinical laboratories, it has also demonstrated that performance within a laboratory is overall very consistent. Accordingly, the availability of defined BCR/ABL RNAs may facilitate the validation of all phases of quantitative BCR/ABL analysis and may be extremely useful as a tool for monitoring assay performance. Ongoing analyses of these materials, along with the development of additional control materials, may solidify consensus around their application in routine laboratory testing and possible integration in worldwide efforts to standardize quantitative BCR/ABL testing.

Decreased thermal conductance during the luteal phase of the menstrual cycle in women.

To study the influence of the menstrual cycle on whole body thermal balance and on thermoregulatory mechanisms, metabolic heat production (M) was measured by indirect calorimetry and total heat losses (H) were measured by direct calorimetry in nine women during the follicular (F) and the luteal (L) phases of the menstrual cycle. The subjects were studied while exposed for 90 min to neutral environmental conditions (ambient temperature 28 degrees C, relative humidity 40%) in a direct calorimeter. The values of M and H were not modified by the phase of the menstrual cycle. Furthermore, in both phases the subjects were in thermal equilibrium because M was similar to H (69.7 +/- 1.8 and 72.1 +/- 1.8 W in F and 70.4 +/- 1.9 and 71.4 +/- 1.7 W in L phases, respectively). Tympanic temperature (Tty) was 0.24 +/- 0.07 degrees C higher in the L than in the F phase (P less than 0.05), whereas mean skin temperature (Tsk) was unchanged. Calculated skin thermal conductance (Ksk) was lower in the L (17.9 +/- 0.6 W.m-2.degrees C-1) than in the F phase (20.1 +/- 1.1 W.m-2.degrees C-1; P less than 0.05). Calculated skin blood flow (Fsk) was also lower in the L (0.101 +/- 0.008 l.min-1.m-2) than in the F phase (0.131 +/- 0.015 l.min-1.m-2; P less than 0.05). Differences in Tty, Ksk, and Fsk were not correlated with changes in plasma progesterone concentration. It is concluded that, during the L phase, a decreased thermal conductance in women exposed to a neutral environment allows the maintenance of a higher internal temperature.

De novo T cell generation and cell cycle analysis of CD4 and CD8 T cells during HIV-disease

RESUME POUR UN LARGE PUBLIC Parmi les globules blancs, les lymphocytes T 004 jouent un rôle primordial dans la coordination de la réponse immunitaire contre les pathogènes et les lymphocytes T CD8 dans leur élimination. Lors d'une infection par le virus de l'immunodéficience humaine (VIH-1), non seulement les cellules T CD4 sont les principales cibles d'infections, mais aussi elles disparaissent progressivement tout au long de la maladie. Ce phénomène, appelé aussi épuisement des lymphocytes T CD4, est la principale cause provoquant le Syndrome d'Immunodéficience Acquise (SIDA). Malgré de grands efforts de recherche, nous ne sommes toujours pas en mesure de dire si ce phénomène est dû à un défaut dans la production de nouvelles cellules ou à une destruction massive de cellules en circulation. Dans cette étude, nous nous proposions, dans un premier temps, de comparer la production de nouvelles cellules T CD4 et CD8 chez des individus VIH-négatifs et positifs. Les cellules nouvellement produites portent un marqueur commun que l'on appelle TREC et qui est facilement mesurable. En considérant des paramètres cliniques, nous étions en mesure de déterminer le niveau de TRECs de cellules T CD4 et CD8 dans différentes phases de la maladie. De là, nous avons pu déterminer que le niveau de TREC est toujours plus bas dans les cellules T CD8 de patients VIH-positifs comparativement à notre groupe contrôle. Nous avons pu déterminer par une analyse ultérieure que cette différence est due à une forte prolifération de ces cellules chez les patients VIH-positifs, ce qui a pour effet de diluer ce marqueur. En revanche, la production de nouvelles cellules T CD4 chez des patients VIH-positifs est accentuée lors de la phase précoce de la maladie et largement réprimée lors de la phase tardive. Dans un second temps, nous avons effectué une analyse à grande échelle de l'expression de gènes associés à la division cellulaire sur des lymphocytes T CD4 et CD8 d'individus VIH-¬positifs et négatifs, avec comme contrôle des cellules proliférant in vitro. De cette étude, nous avons pu conclure que les cellules T CD8 de patients VIH-positifs étaient en état de prolifération, alors que les lymphocytes T CD4 présentaient des défauts majeurs conduisant à un arrêt de la division cellulaire. Nos résultats montrent que la capacité à produire de nouvelles cellules chez des patients VIH¬positifs reste active longtemps pendant la maladie, mais que l'incapacité des cellules T CD4 à proliférer peut enrayer la reconstitution immunitaire chez ces individus. ABSTRACT The hallmark of HIV-1 infection is the depletion of CD4 T cells. Despite extensive investigation, the mechanisms responsible for the loss of CD4 T cells have been elucidated only partially. In particular, it remains controversial whether CD4 T cell depletion results from a defect in T cell production or from a massive peripheral destruction. In this study, de novo T cell generation has been investigated by measuring T cell receptor rearrangement excision circles (TRECs) on large cohorts of HIV-negative (N=120) and HIV-1 infected (N=298) individuals. Analysis of TREC levels was performed in HIV-infected subjects stratified by the stage of HIV disease based on CD4 T cell counts (early: >500 CD4 T cells/µl; intermediate: <500>200; late: <200) and by age (20 to 60 years, n = 259). Our data show that TREC levels in CD8 T cells were significantly lower in HIV-infected subjects at any stage of disease compared to the control group. In contrast, TREC levels in CD4 T cells were significantly higher in HIV-infected subjects at early stages disease while no significant differences were observed at intermediate stages of the disease and were severely reduced only at late stages of disease. To investigate further the status of cell cycle in peripheral CD4 and CD8 T cells in HIV-1 infections, we determined the pattern of gene expression with the microarray technology. In particular, CD4 and CD8 T cells of HIV-1 infected and HIV-negative subjects were analysed by Cell Cycle cDNA expression array. The patterns of gene expression were compared to in vitro stimulated CD4 and CD8 T cells and this analysis showed that CD8 T cells of HIV-1 infected subjects had a pattern of gene expression very similar to that of in vitro stimulated CD8 T cells thus indicating ongoing cell cycling. In contrast, CD4 T cells of HIV-1 infected subjects displayed a complex pattern of gene expression. In fact, CD4 T cells expressed high levels of genes typically associated with cell activation, but low levels of cell cycle genes. Therefore, these results indicated that activated CD4 T cells of HIV-1 infected subjects were in cell cycle arrest. Taking together these results indicate that thymus function is preserved for long time during HIV- 1 infection and the increase observed in early stage disease may represent a compensatory mechanism to the depletion of CD4 T cells. However, we provide evidence for a cell cycle arrest of peripheral CD4 T cells that may prevent potentially the replenishment of CD4 T cells. RESUME Les mécanismes responsables de la perte des lymphocytes T CD4 lors de l'infection pas VIH n'ont été élucidés que partiellement. Nous ne savons toujours pas si l'épuisement des lymphocytes T CD4 résulte d'un défaut dans la production de cellules ou d'une destruction périphérique massive. Dans cette étude, la production de cellules T a été étudiée en mesurant les cercles d'excision générés lors du réarrangement du récepteur au cellules T (TRECs) chez des individus VIH-négatifs (N=120) et VIH-1 positifs (N=298). L'analyse des niveaux de TREC a été faite chez sujets HIV-infectés en considérant les phases de la maladie sur la base des comptes CD4 (phase précoce: > 500 cellules CD4/µl; intermédiaire: < 500>200; tardive: < 200) et par âge. Nos données démontrent que les niveaux de TRECs des cellules T CD8 étaient significativement plus bas chez les sujets VIH-1 infectés, à tous les stades de la maladie comparativement au groupe contrôle. En revanche, les niveaux de TRECs des cellules T CD4 étaient significativement plus élevés chez les sujets VIH-1 infectés durant la phase précoce de la maladie, tandis qu'aucune différence significative n'était observée durant la phase intermédiaire et étaient très réduits dans la phase tardive. Dans une deuxième partie, nous avons utilisé la technique des biopuces à d'ADN complémentaire pour analyser la régulation du cycle cellulaire chez les lymphocytes T CD4 et CD8 périphériques lors d'une infection au VIH-1. Des profils d'expression ont été déterminés et comparés à ceux de cellules T CD4 et CD8 stimulées in vitro, démontrant que les cellules T CD8 des sujets VIH-positifs avaient un profil d'expression très semblable à celui des cellules stimulées in vitro en prolifération. En revanche, les lymphocytes T CD4 des sujets VIH-1 positifs avaient un profil d'expression de gène plus complexe. En fait, leur profil montrait une sur- expression de gènes associés à une activation cellulaire, mais une sous-expression de ceux induisant une division. Ainsi, ces résultats indiquent que les lymphocytes T CD4 d'individus VIH-positifs présentent des dérégulations qui conduisent à un arrêt du cycle cellulaire. Ces résultats montrent que la fonction thymique est préservée longtemps pendant l'infection au VIH-1 et que l'augmentation de la quantité de TRECs dans la phase précoce de la maladie peut représenter un mécanisme compensatoire à l'épuisement des cellules T CD4. Cependant, nous démontrons aussi un clair dysfonctionnement du cycle cellulaire chez les cellules T CD4 d'individus infectés par VIH-1 ce qui peut enrayer la reconstitution du système immunitaire.

Cycle: White under Black. Works from the imperceptible / 3. Freya Powell: I’ll smile and I’m not sad, and other past presents

The video installations of Freya Powell's first exhibition in Barcelona call for an analysis of the links between memory and the archive, between compilation, registration, and the traces of History. Powell's work establishes a fine link between the memory of those sentenced to death in the United States, the memory of the Second World War, the artist's own memory, and the different world maps produced by colonial history. This link forces us to take into account our own connection not only with the voices and words that have been archived, but also with those voices that we want to hear and register.

Histological description of seminiferous epithelium and cycle length of spermatogenesis in the water shrew Neomys fodiens (Mammalia: Soricidae).

Recently, we examined the spermatogenesis cycle length in two shrews species, Sorex araneus characterized by a very high metabolic rate and a polyandric mating system (sperm competition) resulting in a short cycle and Crocidura russula characterized by a much lower metabolic rate and a monogamous mating system showing a longer cycle. In this study, we investigated the spermatogenesis cycle in Neomys fodiens showing an intermediate metabolic rate. We described the stages of seminiferous epithelium according to the spermatid morphology method and we calculated the cycle length of spermatogenesis using incorporation of 5-bromodeoxyuridine into DNA of the germ cells. Twelve males were injected intraperitoneally with 5-bromodeoxyuridine, and the testes were collected. For cycle length determination, we applied a recently developed statistical method. The calculated cycle length is 8.69 days and the total duration of spermatogenesis based on 4.5 cycles is approximately 39.1 days, intermediate between the duration of spermatogenesis of S. araneus (37.6 days) and C. russula (54.5 days) and therefore congruent with both the metabolic rate hypothesis and the sperm competition hypothesis. Relative testes size of 1.4% of body mass indicates a promiscuous mating system.

Relationships of basal metabolic rate, relative testis size and cycle length of spermatogenesis in shrews (Mammalia, Soricidae).

The aim of the present study was to determinate the cycle length of spermatogenesis in three species of shrew, Suncus murinus, Sorex coronatus and Sorex minutus, and to assess the relative influence of variation in basal metabolic rate (BMR) and mating system (level of sperm competition) on the observed rate of spermatogenesis, including data of shrew species studied before (Sorex araneus, Crocidura russula and Neomys fodiens). The dynamics of sperm production were determined by tracing 5-bromodeoxyuridine in the DNA of germ cells. As a continuous scaling of mating systems is not evident, the level of sperm competition was evaluated by the significantly correlated relative testis size (RTS). The cycle durations estimated by linear regression were 14.3 days (RTS 0.3%) in Suncus murinus, 9.0 days (RTS 0.5%) in Sorex coronatus and 8.5 days (RTS 2.8%) in Sorex minutus. In regression and multiple regression analyses including all six studied species of shrew, cycle length was significantly correlated with BMR (r2=0.73) and RTS (r2=0.77). Sperm competition as an ultimate factor obviously leads to a reduction in the time of spermatogenesis in order to increase sperm production. BMR may act in the same way, independently or as a proximate factor, revealed by the covariation, but other factors (related to testes size and thus to mating system) may also be involved.

Contributions of the peroxisome and β-oxidation cycle to biotin synthesis in fungi.

The first step in the synthesis of the bicyclic rings of D-biotin is mediated by 8-amino-7-oxononanoate (AON) synthase, which catalyzes the decarboxylative condensation of l-alanine and pimelate thioester. We found that the Aspergillus nidulans AON synthase, encoded by the bioF gene, is a peroxisomal enzyme with a type 1 peroxisomal targeting sequence (PTS1). Localization of AON to the peroxisome was essential for biotin synthesis because expression of a cytosolic AON variant or deletion of pexE, encoding the PTS1 receptor, rendered A. nidulans a biotin auxotroph. AON synthases with PTS1 are found throughout the fungal kingdom, in ascomycetes, basidiomycetes, and members of basal fungal lineages but not in representatives of the Saccharomyces species complex, including Saccharomyces cerevisiae. A. nidulans mutants defective in the peroxisomal acyl-CoA oxidase AoxA or the multifunctional protein FoxA showed a strong decrease in colonial growth rate in biotin-deficient medium, whereas partial growth recovery occurred with pimelic acid supplementation. These results indicate that pimeloyl-CoA is the in vivo substrate of AON synthase and that it is generated in the peroxisome via the β-oxidation cycle in A. nidulans and probably in a broad range of fungi. However, the β-oxidation cycle is not essential for biotin synthesis in S. cerevisiae or Escherichia coli. These results suggest that alternative pathways for synthesis of the pimelate intermediate exist in bacteria and eukaryotes and that Saccharomyces species use a pathway different from that used by the majority of fungi.

Role of seipin in lipid droplet morphology and hepatitis C virus life cycle.

Infectious hepatitis C virus (HCV) particle assembly starts at the surface of lipid droplets, cytoplasmic organelles responsible for neutral fat storage. We analysed the relationship between HCV and seipin, a protein involved in lipid droplet maturation. Although seipin overexpression did not affect the total mean volume occupied by lipid droplets nor the total triglyceride and cholesterol ester levels per cell, it caused an increase in the mean diameter of lipid droplets by 60 %, while decreasing their total number per cell. The latter two effects combined resulted in a 34 % reduction of the total outer surface area of lipid droplets per cell, with a proportional decrease in infectious viral particle production, probably due to a defect in particle assembly. These results suggest that the available outer surface of lipid droplets is a critical factor for HCV release, independent of the neutral lipid content of the cell.

Study of the incorporation and the anti-tumour efficacy of radio-iododeoxyuridine according to the cellular cycle and in presence of synthesis inhibitor of thymidine

Résumé La iododeoxyuridine (IdUrd), une fois marqué au 123I ou au 125I, est un agent potentiel pour des thérapies par rayonnements Auger. Cependant, des limitations restreignent son incorporation dans l'ADN. Afin d'augmenter celle-ci, différents groupes ont étudié la fluorodeoxyuridine (FdUrd), qui favorise l'incorporation d'analogue de la thymidine, sans toutefois parvenir à une toxicité associé plus importante. Dans notre approche, 3 lignées cellulaires de glioblastomes humains et une lignée de cancer ovarien ont été utilisées. Nous avons observé, 16 à 24 h après un court pré-traitement à la FdUrd, un fort pourcentage de cellules s'accumulant en phase S. Plus qu'une accumulation, c'était une synchronisation des cellules, celles-ci restant capables d'incorporer la radio-IdIrd et repartant dans le cycle cellulaire. De plus, ces cellules accumulées après un pré-traitement à la FdUrd étaient plus radio-sensibles. Après le même intervalle de 16 à 24 h suivant la FdUrd, les 4 lignées cellulaires ont incorporé des taux plus élevés de radio-IdUrd que sans ce prétraitement. Une corrélation temporelle entre l'accumulation des cellules en phase S et la forte incorporation de radio-IdUrd a ainsi été révélée 16 à 24 h après pré-traitement à la FdUrd. Les expériences de traitement par rayonnements Auger sur les cellules accumulées en phase S ont montré une augmentation significative de l'efficacité thérapeutique de 125I-IdUrd comparé aux cellules non prétraitées à la FdUrd. Une première estimation a permis de déterminer que 100 désintégrations de 125I par cellules étant nécessaires afin d'atteindre l'efficacité thérapeutique. De plus, p53 semble jouer un rôle dans l'induction directe de mort cellulaire après des traitements par rayonnements Auger, comme indiqué par les mesures par FACS d'apoptose et de nécrose 24 et 48 h après le traitement. Concernant les expériences in vivo, nous avons observé une incorporation marquée de la radio-IdUrd dans l'ADN après un pré-traitement à la FdUrd dans un model de carcinomatose ovarienne péritonéale. Une augmentation encore plus importante a été observée après injection intra-tumorale dans des transplants sous-cutanés de glioblastomes sur des souris nues. Ces modèles pourraient être utilisés pour de plus amples études de diffusion de radio-IdUrd et de thérapie par rayonnement Auger. En conclusion, ce travail montre une première application réussie de la FdUrd afin d'accroître l'efficacité de la radio-IdUrd par traitements aux rayonnements Auger. La synchronisation des cellules en phase S combinée avec la forte incorporation de radio-IdUrd dans l'ADN différées après un pré-traitement à la FdUrd ont montré le gain thérapeutique attendu in vitro. De plus, des études in vivo sont tout indiquées après les observations encourageantes d'incorporation de radio-IdUrd dans les models de transplants sous-cutanés de glioblastomes et de tumeurs péritonéales ovariennes. Summary Iododeoxyuridine (IdUrd), labelled with 123I or 125I, could be a potential Auger radiation therapy agent. However, limitations restrict its DNA incorporation in proliferating cells. Therefore, fluorodeoxyuridine (FdUrd), which favours incorporation of thymidine analogues, has been studied by different groups in order to increase radio-IdUrd DNA incorporation, however therapeutic efficacy increase could not be reached. In our approach, 3 human glioblastoma cell lines with different p53 expression and one ovarian cancer line were pre-treated with various FdUrd conditions. We observed a high percentage of cells accumulating in early S phase 16 to 24 h after a short and non-toxic FdUrd pre-treatment. More than an accumulation, this was a synchronization, cells remaining able to incorporate radio-IdUrd and re-entering the cell cycle. Furthermore, the S phase accumulated cells post FdUrd pre-treatment were more radiosensitive. After the same delay of 16 to 24 h post FdUrd pre-treatment, the 4 cell lines were incorporating higher rates of radio-IdUrd compared with untreated cells. A time correlation between S phase accumulation and high radio-IdUrd incorporation was therefore revealed 16 to 24 h post FdUrd pre-treatment. Auger radiation treatment experiments performed on S phase enriched cells showed a significant increase of killing efficacy of 125I-IdUrd compared with cells not pre-treated with FdUrd. A first estimation indicates further that about 100 125I decays were required to reach killing in the targeted cells. Moreover, p53 might play a role on the direct induction of cell death pathways after Auger radiation treatments, as indicated by differential apoptosis and necrosis induction measured by FACS 24 and 48 h after treatment initiation. Concerning in vivo results, we observed a marked DNA incorporation increase of radio-IdUrd after FdUrd pre-treatment in peritoneal carcinomatosis in SCID mice. Even higher incorporation increase was observed after intra-tumoural injection of radio-IdUrd in subcutaneous glioblastoma transplants in nude mice. These tumour models might be further useful for diffusion of radio-IdUrd and Auger radiation therapy studies. In conclusion, these data show a first successful application of thymidine synthesis inhibition able to increase the efficacy of radio-IdUrd Auger radiation treatment. The S phase synchronization combined with a high percentage DNA incorporation of radio-IdUrd delayed post FdUrd pre-treatment provided the expected therapeutic gain in vitro. Further in vivo studies are indicated after the observations of encouraging radio-IdUrd uptake experiments in glioblastoma subcutaneous xenografts and in an ovarian peritoneal carcinomatosis model.

Life cycle analysis and life cyle impact assessment methodologies: a state of the art

Life cycle analysis (LCA) is a comprehensive method for assessing the environmental impact of a product or an activity over its entire life cycle. The purpose of conducting LCA studies varies from one application to another. Different applications use LCA for different purposes. In general, the main aim of using LCA is to reduce the environmental impact of products through guiding the decision making process towards more sustainable solutions. The most critical phase in an LCA study is the Life Cycle Impact Assessment (LCIA) where the life cycle inventory (LCI) results of the considered substances related to the study of a certain system are transformed into understandable impact categories that represent the impact on the environment. In this research work, a general structure clarifying the steps that shall be followed ir order to conduct an LCA study effectively is presented. These steps are based on the ISO 14040 standard framework. In addition, a survey is done on the most widely used LCIA methodologies. Recommendations about possible developments and suggetions for further research work regarding the use of LCA and LCIA methodologies are discussed as well.

Applying the principles of life cycle assessment and costing in process modeling to examine profit-making capability

Static process simulation has traditionally been used to model complex processes for various purposes. However, the use of static processsimulators for the preparation of holistic examinations aiming at improving profit-making capability requires a lot of work because the production of results requires the assessment of the applicability of detailed data which may be irrelevant to the objective. The relevant data for the total assessment gets buried byirrelevant data. Furthermore, the models do not include an examination of the maintenance or risk management, and economic examination is often an extra property added to them which can be performed with a spreadsheet program. A process model applicable to holistic economic examinations has been developed in this work. The model is based on the life cycle profit philosophy developed by Hagberg and Henriksson in 1996. The construction of the model has utilized life cycle assessment and life cycle costing methodologies with a view to developing, above all, a model which would be applicable to the economic examinations of complete wholes and which would require the need for information focusing on aspects essential to the objectives. Life cycle assessment and costing differ from each other in terms of the modeling principles, but the features of bothmethodologies can be used in the development of economic process modeling. Methods applicable to the modeling of complex processes can be examined from the viewpoint of life cycle methodologies, because they involve the collection and management of large corpuses of information and the production of information for the needs of decision-makers as well. The results of the study shows that on the basis of the principles of life cycle modeling, a process model can be created which may be used to produce holistic efficiency examinations on the profit-making capability of the production line, with fewer resources thanwith traditional methods. The calculations of the model are based to the maximum extent on the information system of the factory, which means that the accuracyof the results can be improved by developing information systems so that they can provide the best information for this kind of examinations.

On the Reversed Brayton Cycle with High Speed Machinery

This work was carried out in the laboratory of Fluid Dynamics, at Lappeenranta University of Technology during the years 1991-1996. The research was a part of larger high speed technology development research. First, there was the idea of making high speed machinery applications with the Brayton cycle. There was a clear need to deepen theknowledge of the cycle itself and to make a new approach in the field of the research. Also, the removal of water from the humid air seemed very interesting. The goal of this work was to study methods of designing high speed machinery to the reversed Brayton cycle, from theoretical principles to practical applications. The reversed Brayton cycle can be employed as an air dryer, a heat pump or a refrigerating machine. In this research the use of humid air as a working fluid has an environmental advantage, as well. A new calculation method for the Braytoncycle is developed. In this method especially the expansion process in the turbine is important because of the condensation of the water vapour in the humid air. This physical phenomena can have significant effects on the level of performance of the application. Also, the influence of calculating the process with actual, achievable process equipment efficiencies is essential for the development of the future machinery. The above theoretical calculations are confirmed with two different laboratory prototypes. The high speed machinery concept allows one to build an application with only one rotating shaft including all the major parts: the high speed motor, the compressor and the turbine wheel. The use of oil free bearings and high rotational speed outlines give several advantages compared to conventional machineries: light weight, compact structure, safe operation andhigher efficiency at a large operational region. There are always problems whentheory is applied to practice. The calibrations of pressure, temperature and humidity probes were made with care but still measurable errors were not negligible. Several different separators were examined and in all cases the content of the separated water was not exact. Due to the compact sizes and structures of the prototypes, the process measurement was slightly difficult. The experimental results agree well with the theoretical calculations. These experiments prove the operation of the process and lay a ground for the further development. The results of this work give very promising possibilities for the design of new, commercially competitive applications that use high speed machinery and the reversed Brayton cycle.