New approaches to improve the cord blood unit hematopoietic progenitor cell content

Cord blood is a well-established alternative to bone marrow and peripheral blood stem cell transplantation. To this day, over 400 000 unrelated donor cord blood units have been stored in cord blood banks worldwide. To enable successful cord blood transplantation, recent efforts have been focused on finding ways to increase the hematopoietic progenitor cell content of cord blood units. In this study, factors that may improve the selection and quality of cord blood collections for banking were identified. In 167 consecutive cord blood units collected from healthy full-term neonates and processed at a national cord blood bank, mean platelet volume (MPV) correlated with the numbers of cord blood unit hematopoietic progenitors (CD34+ cells and colony-forming units); this is a novel finding. Mean platelet volume can be thought to represent general hematopoietic activity, as newly formed platelets have been reported to be large. Stress during delivery is hypothesized to lead to the mobilization of hematopoietic progenitor cells through cytokine stimulation. Accordingly, low-normal umbilical arterial pH, thought to be associated with perinatal stress, correlated with high cord blood unit CD34+ cell and colony-forming unit numbers. The associations were closer in vaginal deliveries than in Cesarean sections. Vaginal delivery entails specific physiological changes, which may also affect the hematopoietic system. Thus, different factors may predict cord blood hematopoietic progenitor cell numbers in the two modes of delivery. Theoretical models were created to enable the use of platelet characteristics (mean platelet volume) and perinatal factors (umbilical arterial pH and placental weight) in the selection of cord blood collections with high hematopoietic progenitor cell counts. These observations could thus be implemented as a part of the evaluation of cord blood collections for banking. The quality of cord blood units has been the focus of several recent studies. However, hemostasis activation during cord blood collection is scarcely evaluated in cord blood banks. In this study, hemostasis activation was assessed with prothrombin activation fragment 1+2 (F1+2), a direct indicator of thrombin generation, and platelet factor 4 (PF4), indicating platelet activation. Altogether three sample series were collected during the set-up of the cord blood bank as well as after changes in personnel and collection equipment. The activation decreased from the first to the subsequent series, which were collected with the bank fully in operation and following international standards, and was at a level similar to that previously reported for healthy neonates. As hemostasis activation may have unwanted effects on cord blood cell contents, it should be minimized. The assessment of hemostasis activation could be implemented as a part of process control in cord blood banks. Culture assays provide information about the hematopoietic potential of the cord blood unit. In processed cord blood units prior to freezing, megakaryocytic colony growth was evaluated in semisolid cultures with a novel scoring system. Three investigators analyzed the colony assays, and the scores were highly concordant. With such scoring systems, the growth potential of various cord blood cell lineages can be assessed. In addition, erythroid cells were observed in liquid cultures of cryostored and thawed, unseparated cord blood units without exogenous erythropoietin. This was hypothesized to be due to the erythropoietic effect of thrombopoietin, endogenous erythropoietin production, and diverse cell-cell interactions in the culture. This observation underscores the complex interactions of cytokines and supporting cells in the heterogeneous cell population of the thawed cord blood unit.

Content of zinc, iron and their absorption inhibitors in Nicaraguan common beans (Phaseolus vulgaris L.).

Protein-energy malnutrition and mineral deficiencies are two of the three forms of nutritional deficiencies that affect most developing countries due to inadequate access to food and diets based on a sole crop. Common bean (Phaseolus vulgaris L.) is the staple crop of Nicaragua and it has the potential to improve the nutritional status of the poorest group of the nation. Its high content of both protein and nonhaem iron provides many nutrients, but inhibitors also may prevent absorption of iron and zinc by the human consumer. A proper production chain must be followed to ensure the best grain quality for the consumer. To achieve food security, both production and high nutritional content must be maintained. Four nationally important accessions of common bean, with different harvesting dates, were selected to be submitted to two treatments: to evaluate the impact of storage conditions on the end quality of the grain. The duration of the study was six months with sampling every six weeks, and the two treatments were controlled one stored at 40°C and 75 RH %, and the other was stored in in-situ conditions. Proximate and mineral composition was evaluated as well as tannin, phytate and bioavailability. Significant differences among different accessions were found, being the most significant in protein, Fe and Zn content, tannins and phytate. Protein values ranged from 21-23%. Iron content was 61-81 mg/kg but only 3-4% was bioavailable. Zinc content was 21-25 mg/kg and 10-12% was bioavailable. The concentration of phytate ranged from 8.6-9.6 mg/g while tannin values ranged within 37.7-43.8 mg/g. Storage at high temperatures was demonstrated to have an impact on certain nutritional compounds and proved detrimental to final grain quality. Soluble sugar content and tannin content decreased after six months in both storage conditions, IDF decreased in the in-situ and SDF in the stress. The iron content and bioavailability in INTA Biofortificado were not as outstanding as expected, so experiments should be conducted to compare its iron uptake and delivery with other cultivars.

Water content variations of sandy soil under winter conditions

Yhteenveto: Maankosteusvaihtelut talvella hiekkamaassa

Biomassan energia-arvon nostaminen sekundäärilämmöllä kuivaamalla

Viime aikoina ilmastonmuutos, fossiilisten polttoaineiden väheneminen ja niiden hinnan nousu ovat lisänneet merkittävästi maailmanlaajuista kiinnostusta uusiutuviin energiavaroihin. Suomessa uusiutuvien energialähteiden käytössä on jo pitkään panostettu metsäteollisuuden sivutuotevirtana tuottamaan puuperäiseen biomassaan, jota metsäteollisuus käyttää energiantuotantoonsa. Metsäteollisuuden jätevesien käsittelyssä syntyy erilaisia lietteitä, jotka joko uusiokäytetään tai hävitetään polttamalla tai sijoittamalla kaatopaikalle. Erityisesti biolietteiden uusiokäyttö on hankalaa ja kaatopaikkasijoitus tulevaisuudessa mahdotonta tai ainakin kustannuksiltaan kohtuutonta. Käytännössä liete hävitetään polttamalla ja kuivaamalla siitä tulee polttoaine. Lietteiden energiakäyttö on järkevin tapa hävittää jäteliete. Lietteiden korkean vesipitoisuuden vuoksi ne tulee kuitenkin kuivata ennen polttoa. Lietteen kuivaaminen sekundäärienergiavirralla eli metsäteollisuusprosesseissa sivutuotteena muodostuvalla ns. hukkalämmöllä lisää lietteen poltosta saatavaa energiamäärää ja korvaa fossiilisten polttoaineiden käyttöä. Tutkimuksen tavoitteena oli selvittää lietteen kuivaukseen optimaalisin kuoren ja lietteen seossuhde eri kuivausparametrejä vaihdellen. Kokeellinen työ aloitettiin rakentamalla energiatekniikan koehalliin laboratoriokokoluokan kiintopetikuivuri, jossa kuivumista tutkittiin puhaltamalla polttoainepedin läpi lämmitettyä ilmaa. Kuivattavina polttoaineina olivat kuoren ja lietteen seos tai pelkkä kuori ja liete erilaisilla massoilla ja erilaisilla prosenttisilla suhteilla ja erilaisissa lämpötiloissa. Kuivumiskäyrien määritys perustui massanmuutokseen. Koelaitteessa olivat anturit lämpötilan mittausta varten, jotta lämpötila saatiin säädettyä ja seurattua kokeen edellyttämällä tavalla. Lämpötilat ja painonmuutokset tallentuivat koetta tehdessä tietokoneelle. Kuivauskokeet osoittivat, että liete-kuori seos kuivuu hyvin kiintopedissä kun lietteen massaosuus seoksessa on korkeintaan 50 %. Lietteen massaosuuden ollessa tätä suurempi kuivaaminen ei enää ole tehokasta, mikä johtuu luultavasti ilman suuresta kanavoitumisesta kuivauspedissä. Kuorta kuivatessa lämpötilan nosto 50 °C:stä 70 °C:een oli huomattavasti tehokkaampaa kuin 70 °C:stä 90 °C:een, ajallisesti ero oli noin kaksinkertainen.

Psychologically-Based and Content-Oriented Experience in Entertainment Virtual Environments

In daily life, rich experiences evolve in every environmental and social interaction. Because experience has a strong impact on how people behave, scholars in different fields are interested in understanding what constitutes an experience. Yet even if interest in conscious experience is on the increase, there is no consensus on how such experience should be studied. Whatever approach is taken, the subjective and psychologically multidimensional nature of experience should be respected. This study endeavours to understand and evaluate conscious experiences. First I intro-duce a theoretical approach to psychologically-based and content-oriented experience. In the experiential cycle presented here, classical psychology and orienting-environmental content are connected. This generic approach is applicable to any human-environment interaction. Here I apply the approach to entertainment virtual environments (VEs) such as digital games and develop a framework with the potential for studying experiences in VEs. The development of the methodological framework included subjective and objective data from experiences in the Cave Automatic Virtual Environment (CAVE) and with numerous digital games (N=2,414). The final framework consisted of fifteen factor-analytically formed subcomponents of the sense of presence, involvement and flow. Together, these show the multidimensional experiential profile of VEs. The results present general experiential laws of VEs and show that the interface of a VE is related to (physical) presence, which psychologically means attention, perception and the cognitively evaluated realness and spatiality of the VE. The narrative of the VE elicits (social) presence and involvement and affects emotional outcomes. Psychologically, these outcomes are related to social cognition, motivation and emotion. The mechanics of a VE affect the cognitive evaluations and emotional outcomes related to flow. In addition, at the very least, user background, prior experience and use context affect the experiential variation. VEs are part of many peoples lives and many different outcomes are related to them, such as enjoyment, learning and addiction, depending on who is making the evalua-tion. This makes VEs societally important and psychologically fruitful to study. The approach and framework presented here contribute to our understanding of experiences in general and VEs in particular. The research can provide VE developers with a state-of-the art method (www.eveqgp.fi) that can be utilized whenever new product and service concepts are designed, prototyped and tested.

Introduction of high-content screening method for studying drug-induced mitochondrial dysfunction in hepatocytes

Drug induced liver injury is one of the frequent reasons for the drug removal from the market. During the recent years there has been a pressure to develop more cost efficient, faster and easier ways to investigate drug-induced toxicity in order to recognize hepatotoxic drugs in the earlier phases of drug development. High Content Screening (HCS) instrument is an automated microscope equipped with image analysis software. It makes the image analysis faster and decreases the risk for an error caused by a person by analyzing the images always in the same way. Because the amount of drug and time needed in the analysis are smaller and multiple parameters can be analyzed from the same cells, the method should be more sensitive, effective and cheaper than the conventional assays in cytotoxicity testing. Liver cells are rich in mitochondria and many drugs target their toxicity to hepatocyte mitochondria. Mitochondria produce the majority of the ATP in the cell through oxidative phosphorylation. They maintain biochemical homeostasis in the cell and participate in cell death. Mitochondria is divided into two compartments by inner and outer mitochondrial membranes. The oxidative phosphorylation happens in the inner mitochondrial membrane. A part of the respiratory chain, a protein called cytochrome c, activates caspase cascades when released. This leads to apoptosis. The aim of this study was to implement, optimize and compare mitochondrial toxicity HCS assays in live cells and fixed cells in two cellular models: human HepG2 hepatoma cell line and rat primary hepatocytes. Three different hepato- and mitochondriatoxic drugs (staurosporine, rotenone and tolcapone) were used. Cells were treated with the drugs, incubated with the fluorescent probes and then the images were analyzed using Cellomics ArrayScan VTI reader. Finally the results obtained after optimizing methods were compared to each other and to the results of the conventional cytotoxicity assays, ATP and LDH measurements. After optimization the live cell method and rat primary hepatocytes were selected to be used in the experiments. Staurosporine was the most toxic of the three drugs and caused most damage to the cells most quickly. Rotenone was not that toxic, but the results were more reproducible and thus it would serve as a good positive control in the screening. Tolcapone was the least toxic. So far the conventional analysis of cytotoxicity worked better than the HCS methods. More optimization needs to be done to get the HCS method more sensitive. This was not possible in this study due to time limit.

On the Modal Content of A Posteriori Necessities

This paper challenges the Kripkean interpretation of a posteriori necessities. It will be demonstrated, by an analysis of classic examples, that the modal content of supposed a posteriori necessities is more complicated than the Kripkean line suggests. We will see that further research is needed concerning the a priori principles underlying all a posteriori necessities. In the course of this analysis it will emerge that the modal content of a posteriori necessities can be best described in terms of a Finean conception of modality – by giving essences priority over modality. The upshot of this is that we might be able to establish the necessity of certain supposed a posteriori necessities by a priori means.

Interfacial Phenomena in Pharmaceutical Low Moisture Content Powder Processing

Powders are essential materials in the pharmaceutical industry, being involved in majority of all drug manufacturing. Powder flow and particle size are central particle properties addressed by means of particle engineering. The aim of the thesis was to gain knowledge on powder processing with restricted liquid addition, with a primary focus on particle coating and early granule growth. Furthermore, characterisation of this kind of processes was performed. A thin coating layer of hydroxypropyl methylcellulose was applied on individual particles of ibuprofen in a fluidised bed top-spray process. The polymeric coating improved the flow properties of the powder. The improvement was strongly related to relative humidity, which can be seen as an indicator of a change in surface hydrophilicity caused by the coating. The ibuprofen used in the present study had a d50 of 40 μm and thus belongs to the Geldart group C powders, which can be considered as challenging materials in top-spray coating processes. Ibuprofen was similarly coated using a novel ultrasound-assisted coating method. The results were in line with those obtained from powders coated in the fluidised bed process mentioned above. It was found that the ultrasound-assisted method was capable of coating single particles with a simple and robust setup. Granule growth in a fluidised bed process was inhibited by feeding the liquid in pulses. The results showed that the length of the pulsing cycles is of importance, and can be used to adjust granule growth. Moreover, pulsed liquid feed was found to be of greater significance to granule growth in high inlet air relative humidity. Liquid feed pulsing can thus be used as a tool in particle size targeting in fluidised bed processes and in compensating for changes in relative humidity of the inlet air. The nozzle function of a two-fluid external mixing pneumatic nozzle, typical for small scale pharmaceutical fluidised bed processes, was studied in situ in an ongoing fluidised bed process with particle tracking velocimetry. It was found that the liquid droplets undergo coalescence as they proceed away from the nozzle head. The coalescence was expected to increase droplet speed, which was confirmed in the study. The spray turbulence was studied, and the results showed turbulence caused by the event of atomisation and by the oppositely directed fluidising air. It was concluded that particle tracking velocimetry is a suitable tool for in situ spray characterisation. The light transmission through dense particulate systems was found to carry information on particle size and packing density as expected based on the theory of light scattering by solids. It was possible to differentiate binary blends consisting of components with differences in optical properties. Light transmission showed potential as a rapid, simple and inexpensive tool in characterisation of particulate systems giving information on changes in particle systems, which could be utilised in basic process diagnostics.

Airborne sulphur and lake water acidification in Finland.

Tiivistelmä: Ilman rikkilaskeuma ja järvien happamoituminen Suomessa.

Jatrophanviljely ja maankäyttö Vietnamissa

Biofuels are under discussion all over the world today. There are fears that the farming of biofuel plants hurts food production and weakens the food security of the poor. On the other hand, biofuel production could lessen the green house gas emissions caused by transportation, and it could also spread the profits from fuel markets more evenly between countries. The aim of this thesis is to find out how an oil plant called jatropha curcas L., which is used for biodiesel production, can affect the sustainability of livelihoods in Vietnam from the point of view of land use. Special attention is given to the effects of jatropha farming on food production, land productivity, natural resources of livelihoods and global livelihood. Jatropha belongs to the family Euphorbiaceae, and it grows naturally in tropical and subtropical areas. It can be grown on poor soils, its seeds have high oil content, and it cannot be eaten due to its toxicity. The plant grows naturally in Vietnam, and during the past few years it has also begun to be farmed for making biodiesel. Population growth in Vietnam has slowed down, but the population's standard of living and energy consumption are still rising quickly. An interest in the international biodiesel markets has awoken following Vietnam's opening up to international trade. Jatropha diesel plays a significant part in Vietnam’s clean fuel strategy, and many companies have set up jatropha plantations to produce raw material for biodiesel. Diesel made from jatropha is planned to be used both locally and for export. This thesis uses a theoretical concept of sustainable livelihoods. According to the theory, the resources that people have shape their livelihood possibilities. Farming of jatropha affects the livelihoods of people especially through land use, as land use changes have effects on many of the livelihood resources. In addition to the written sources, the material of the thesis is based on 14 interviews in Vietnam and Finland, and on observation during a field trip to Northern Vietnam in the spring of 2008. The results of the thesis show that jatropha diesel can support the sustainability of livelihoods at different scales if it is produced with deliberation. However, positive results are only possible if decisions are made carefully and more experience is collected. The possibilities of sustainable jatropha farming depend mainly on the previous land use methods and ways of production. Farming of jatropha does not threaten food production in Vietnam if the farming plans are implemented as planned. Jatropha may take some land from cassava, but at the same time, food production can be increased if mixed farming is used on some farms. Plenty of new research information and practical experiences on jatropha farming has to be collected before results of the real sustainability of the farming are ready. Carefully considered continuation and documentation of present and future projects would help to understand the possibilities of jatropha diesel in Vietnam and elsewhere.