Phorbol 12-myristate 13-acetate induces surface expression of T3 on human immature T cell lines with and without concomitant expression of the T cell antigen receptor complex.

The T3 complex is known to be expressed on the cell surface of mature T cells together with either the alpha-beta heterodimeric T cell receptor (TCR) or the TCR gamma protein. In a number of immature T cell malignancies, however, T3 has been described exclusively in the cytoplasm. We have investigated five such T cell lines with cytoplasmic T3 and could demonstrate by biosynthetic labeling the presence of the alpha and beta chains of the TCR in the cytoplasm of two of them, CEM and Ichikawa. No surface TCR alpha-beta protein could be detected by staining with the WT31 antibody. These observations, therefore, argue against the concept that expression of the TCR alpha chain controls the surface expression of the T3/TCR complex. Interestingly, phorbol 12-myristate 13-acetate (PMA) induced cell surface expression of T3 protein in these two cell lines only. Moreover, on surface-iodinated CEM cells no association of T3 and TCR molecules could be demonstrated after treatment with PMA, and expression of TCR alpha and beta chains was limited to the cytoplasm. In Ichikawa cells, however, PMA induced surface expression of a mature T3/TCR complex. Our findings indicate that separate regulatory mechanisms may exist for the surface expression of the T3 proteins and for the assembly of the T3/TCR complex.

Bayesian Markov-chain-Monte-Carlo inversion of time-lapse cross hole ground-penetrating radar data to characterize the vadose zone at the Arrenaes field site, Denmark

The ground-penetrating radar (GPR) geophysical method has the potential to provide valuable information on the hydraulic properties of the vadose zone because of its strong sensitivity to soil water content. In particular, recent evidence has suggested that the stochastic inversion of crosshole GPR traveltime data can allow for a significant reduction in uncertainty regarding subsurface van Genuchten-Mualem (VGM) parameters. Much of the previous work on the stochastic estimation of VGM parameters from crosshole GPR data has considered the case of steady-state infiltration conditions, which represent only a small fraction of practically relevant scenarios. We explored in detail the dynamic infiltration case, specifically examining to what extent time-lapse crosshole GPR traveltimes, measured during a forced infiltration experiment at the Arreneas field site in Denmark, could help to quantify VGM parameters and their uncertainties in a layered medium, as well as the corresponding soil hydraulic properties. We used a Bayesian Markov-chain-Monte-Carlo inversion approach. We first explored the advantages and limitations of this approach with regard to a realistic synthetic example before applying it to field measurements. In our analysis, we also considered different degrees of prior information. Our findings indicate that the stochastic inversion of the time-lapse GPR data does indeed allow for a substantial refinement in the inferred posterior VGM parameter distributions compared with the corresponding priors, which in turn significantly improves knowledge of soil hydraulic properties. Overall, the results obtained clearly demonstrate the value of the information contained in time-lapse GPR data for characterizing vadose zone dynamics.

Sex differences in lipid and glucose kinetics after ingestion of an acute oral fructose load.

The increase in VLDL TAG concentration after ingestion of a high-fructose diet is more pronounced in men than in pre-menopausal women. We hypothesised that this may be due to a lower fructose-induced stimulation of de novo lipogenesis (DNL) in pre-menopausal women. To evaluate this hypothesis, nine healthy male and nine healthy female subjects were studied after ingestion of oral loads of fructose enriched with 13C6 fructose. Incorporation of 13C into breath CO2, plasma glucose and plasma VLDL palmitate was monitored to evaluate total fructose oxidation, gluconeogenesis and hepatic DNL, respectively. Substrate oxidation was assessed by indirect calorimetry. After 13C fructose ingestion, 44.0 (sd 3.2)% of labelled carbons were recovered in plasma glucose in males v. 41.9 (sd 2.3)% in females (NS), and 42.9 (sd 3.7)% of labelled carbons were recovered in breath CO2 in males v. 43.0 (sd 4.5)% in females (NS), indicating similar gluconeogenesis from fructose and total fructose oxidation in males and females. The area under the curve for 13C VLDL palmitate tracer-to-tracee ratio was four times lower in females (P < 0.05), indicating a lower DNL. Furthermore, lipid oxidation was significantly suppressed in males (by 16.4 (sd 5.2), P < 0.05), but it was not suppressed in females ( -1.3 (sd 4.7)%). These results support the hypothesis that females may be protected against fructose-induced hypertriglyceridaemia because of a lower stimulation of DNL and a lower suppression of lipid oxidation.

A spatially explicit life cycle inventory of the global textile chain

Life cycle analyses (LCA) approaches require adaptation to reflect the increasing delocalization of production to emerging countries. This work addresses this challenge by establishing a country-level, spatially explicit life cycle inventory (LCI). This study comprises three separate dimensions. The first dimension is spatial: processes and emissions are allocated to the country in which they take place and modeled to take into account local factors. Emerging economies China and India are the location of production, the consumption occurs in Germany, an Organisation for Economic Cooperation and Development country. The second dimension is the product level: we consider two distinct textile garments, a cotton T-shirt and a polyester jacket, in order to highlight potential differences in the production and use phases. The third dimension is the inventory composition: we track CO2, SO2, NO (x), and particulates, four major atmospheric pollutants, as well as energy use. This third dimension enriches the analysis of the spatial differentiation (first dimension) and distinct products (second dimension). We describe the textile production and use processes and define a functional unit for a garment. We then model important processes using a hierarchy of preferential data sources. We place special emphasis on the modeling of the principal local energy processes: electricity and transport in emerging countries. The spatially explicit inventory is disaggregated by country of location of the emissions and analyzed according to the dimensions of the study: location, product, and pollutant. The inventory shows striking differences between the two products considered as well as between the different pollutants considered. For the T-shirt, over 70% of the energy use and CO2 emissions occur in the consuming country, whereas for the jacket, more than 70% occur in the producing country. This reversal of proportions is due to differences in the use phase of the garments. For SO2, in contrast, over two thirds of the emissions occur in the country of production for both T-shirt and jacket. The difference in emission patterns between CO2 and SO2 is due to local electricity processes, justifying our emphasis on local energy infrastructure. The complexity of considering differences in location, product, and pollutant is rewarded by a much richer understanding of a global production-consumption chain. The inclusion of two different products in the LCI highlights the importance of the definition of a product's functional unit in the analysis and implications of results. Several use-phase scenarios demonstrate the importance of consumer behavior over equipment efficiency. The spatial emission patterns of the different pollutants allow us to understand the role of various energy infrastructure elements. The emission patterns furthermore inform the debate on the Environmental Kuznets Curve, which applies only to pollutants which can be easily filtered and does not take into account the effects of production displacement. We also discuss the appropriateness and limitations of applying the LCA methodology in a global context, especially in developing countries. Our spatial LCI method yields important insights in the quantity and pattern of emissions due to different product life cycle stages, dependent on the local technology, emphasizing the importance of consumer behavior. From a life cycle perspective, consumer education promoting air-drying and cool washing is more important than efficient appliances. Spatial LCI with country-specific data is a promising method, necessary for the challenges of globalized production-consumption chains. We recommend inventory reporting of final energy forms, such as electricity, and modular LCA databases, which would allow the easy modification of underlying energy infrastructure.

The stereochemistry of the amino acid side chain influences the inflammatory potential of muramyl dipeptide in experimental meningitis.

Intrathecal injections of 50 to 100 micro g of (N-acetylmuramyl-L-alanyl-D-isoglutamine) muramyl dipeptide (MDP)/rabbit dose-dependently triggered tumor necrosis factor alpha (TNF-alpha) secretion (12 to 40,000 pg/ml) preceding the influx of leukocytes in the subarachnoid space of rabbits. Intrathecal instillation of heat-killed unencapsulated R6 pneumococci produced a comparable leukocyte influx but only a minimal level of preceding TNF-alpha secretion. The stereochemistry of the first amino acid (L-alanine) of the MDP played a crucial role with regard to its inflammatory potential. Isomers harboring D-alanine in first position did not induce TNF-alpha secretion and influx of leukocytes. This stereospecificity of MDPs was also confirmed by measuring TNF-alpha release from human peripheral mononuclear blood cells stimulated in vitro. These data show that the inflammatory potential of MDPs depends on the stereochemistry of the first amino acid of the peptide side chain and suggest that intact pneumococci and MDPs induce inflammation by different pathways.

Gene transfer of the Ly-3 chain gene of the mouse CD8 molecular complex: co-transfer with the Ly-2 polypeptide gene results in detectable cell surface expression of the Ly-3 antigenic determinants.

The CD8 molecule is a glycoprotein expressed on a subset of mature T lymphocytes. It has been postulated to be a receptor for class I major histocompatibility complex molecules. In the mouse, CD8 is a heterodimer composed of Ly-2 and Ly-3 chains. We have isolated and analyzed cDNA and cosmid clones corresponding to the Ly-3 subunit. One of the isolated, cosmid clones was subsequently transfected, alone or in combination with the Ly-2 gene, into mouse Ltk- cells. Analysis of the Ly-2,3 molecules expressed at the surface of the double transfectants indicated that they are serologically and biochemically indistinguishable from their normal counterparts expressed on lymphoid cells. Ltk- cells transfected with the Ly-2 gene alone were shown to react with a subset of anti-CD8 monoclonal antibodies whereas Ly-3 transfectants did not stain with any of the anti-Ly-3 antibodies employed in this study. Since at least one of these antibodies (53-5.8) has been previously shown to recognize an epitope which is retained on the Ly-3 subunit after dissociation of the heterodimeric Ly-2,3 complex, these observations suggest that the expression of the Ly-2 polypeptide is required to permit the detectable cell surface expression of the antigenic determinants carried by the Ly-3 subunit.

Kinetics of chronic inflammation in Nile tilapia fed n‑3 and n‑6 essential fatty acids

The objective of this work was to investigate the effect of dietary supplementation with essential fatty acids on the kinetics of macrophage accumulation and giant cell formation in Nile tilapia (Oreochromis niloticus). The supplementation sources were soybean oil (SO, source of omega 6, n‑6) and linseed oil (LO, source of omega 3, n‑3), in the following proportions: 100% SO; 75% SO + 25% LO; 50% SO + 50% LO; 25% SO + 75% LO; and 100% LO (four replicates per treatment). After a feeding period of three months, growth performance was evaluated, and glass coverslips were implanted into the subcutaneous connective tissue of fish, being removed for examination at 2, 4, 6, and 8 days after implantation. Growth performance did not differ between treatments. Fish fed 100% linseed oil diet had the greatest macrophage accumulation and the fastest Langhans cell formation on the sixth day. On the eighth day, Langhans cells were predominant on the coverslips implanted in the fish feed 75 and 100% linseed oil. n‑3 fatty acids may contribute to macrophage recruitment and giant cell formation in fish chronic inflammatory response to foreign body.

Long-term antiretroviral treatment initiated at primary HIV-1 infection affects the size, composition, and decay kinetics of the reservoir of HIV-1-infected CD4 T cells.

Initiation of antiretroviral therapy during the earliest stages of HIV-1 infection may limit the seeding of a long-lasting viral reservoir, but long-term effects of early antiretroviral treatment initiation remain unknown. Here, we analyzed immunological and virological characteristics of nine patients who started antiretroviral therapy at primary HIV-1 infection and remained on suppressive treatment for >10 years; patients with similar treatment duration but initiation of suppressive therapy during chronic HIV-1 infection served as controls. We observed that independently of the timing of treatment initiation, HIV-1 DNA in CD4 T cells decayed primarily during the initial 3 to 4 years of treatment. However, in patients who started antiretroviral therapy in early infection, this decay occurred faster and was more pronounced, leading to substantially lower levels of cell-associated HIV-1 DNA after long-term treatment. Despite this smaller size, the viral CD4 T cell reservoir in persons with early treatment initiation consisted more dominantly of the long-lasting central-memory and T memory stem cells. HIV-1-specific T cell responses remained continuously detectable during antiretroviral therapy, independently of the timing of treatment initiation. Together, these data suggest that early HIV-1 treatment initiation, even when continued for >10 years, is unlikely to lead to viral eradication, but the presence of low viral reservoirs and durable HIV-1 T cell responses may make such patients good candidates for future interventional studies aiming at HIV-1 eradication and cure. IMPORTANCE: Antiretroviral therapy can effectively suppress HIV-1 replication to undetectable levels; however, HIV-1 can persist despite treatment, and viral replication rapidly rebounds when treatment is discontinued. This is mainly due to the presence of latently infected CD4 T cells, which are not susceptible to antiretroviral drugs. Starting treatment in the earliest stages of HIV-1 infection can limit the number of these latently infected cells, raising the possibility that these viral reservoirs are naturally eliminated if suppressive antiretroviral treatment is continued for extremely long periods of time. Here, we analyzed nine patients who started on antiretroviral therapy within the earliest weeks of the disease and continued treatment for more than 10 years. Our data show that early treatment accelerated the decay of infected CD4 T cells and led to very low residual levels of detectable HIV-1 after long-term therapy, levels that were otherwise detectable in patients who are able to maintain a spontaneous, drug-free control of HIV-1 replication. Thus, long-term antiretroviral treatment started during early infection cannot eliminate HIV-1, but the reduced reservoirs of HIV-1 infected cells in such patients may increase their chances to respond to clinical interventions aiming at inducing a drug-free remission of HIV-1 infection.

Legal Issues for FOSS-based Supply Chain Management ¿ Black Duck Software

Open source is typically outside of normal commercial software procurement processes.The Challenges.Increasingly diverse and distributed set of development resources.Little/no visibility into the origins of the software.Supply Chain Comparison: Hardware vs Software.Open source has revolutionized the mobile and device landscape, other industries will follow.Supply chain management techniques from hardware are useful for managing software.SPDX A standard format for communicating a software Bill of Materials across the supply chain.Effective management and control requires training, tools, processes and standards.

Item master management in the engineer-to-order supply chain

Diplomityöntavoitteena on tutkia, kuinka nimiketiedon hallinnalla voidaan parantaa kustannustehokkuutta projektiohjautuvassa toimitusketjussa. Työn kohdeyritys on Konecranes Oyj:n tytäryhtiö Konecranes Heavy Lifting Oy. Nimiketiedon hallinta liittyy läheisesti tuotetiedon hallintaan. Teoriaosassa käsitellään toimitusketjuympäristön tekijöitä, modulaarisuuden ja asiakaskohtaisuuden ongelmallisuutta sekä informaatiovirran vaikutuksia eri toiminnoissa. Yritysosassa vertaillaan konsernitason kahta liiketoiminta-aluetta strategiavalintojen, tuotteiden modulaarisuuden sekä tilaus-toimitusprosessissa liikkuvan nimikeinformaation perusteella. Diplomityön tuloksena annetaan suuntaviivat; nimikemassan eheytykseen, strategisten nimikkeiden tunnistamiseen ja määrittämiseen, nimikkeiden hallintaan sekä master-datan sijoittamiseen tietojärjestelmäympäristöön.

Reversible mitochondrial respiratory chain impairment during symptomatic hyperlactatemia associated with antiretroviral therapy

Direct evidence confirming the hypothesis that a dysfunction of the mitochondrial respiratory chain (MRC) underlies the pathogenesis of hyperlactatemia associated with highly active antiretroviral therapy (HAART) is scarce. We studied mitochondrial DNA (mtDNA) content and MRC function in the skeletal muscle of an HIV-infected patient during an episode of symptomatic hyperlactatemia. Skeletal muscle biopsy was performed during the episode when the patient was symptomatic and 3 months later when the patient was clinically recovered. Assessment of mitochondria was performed using histological, polarographic, spectrophotometrical, and Southern blot and real time PCR DNA quantification methods. The histological study disclosed extensive mitochondrial impairment in the form of ragged-red fibers or equivalents on oxidative reactions. These findings were associated with an increase in mitochondrial content and a decrease in both mitochondrial respiratory capacity and MRC enzyme activities. Mitochondrial DNA content declined to 53% of control values. Mitochondrial abnormalities had almost disappeared later when the patient became asymptomatic. Our findings support the hypothesis that MRC dysfunction stands at the basis of HAART-related hyperlactatemia.

Reversible mitochondrial respiratory chain impairment during symptomatic hyperlactatemia associated with antiretroviral therapy

Direct evidence confirming the hypothesis that a dysfunction of the mitochondrial respiratory chain (MRC) underlies the pathogenesis of hyperlactatemia associated with highly active antiretroviral therapy (HAART) is scarce. We studied mitochondrial DNA (mtDNA) content and MRC function in the skeletal muscle of an HIV-infected patient during an episode of symptomatic hyperlactatemia. Skeletal muscle biopsy was performed during the episode when the patient was symptomatic and 3 months later when the patient was clinically recovered. Assessment of mitochondria was performed using histological, polarographic, spectrophotometrical, and Southern blot and real time PCR DNA quantification methods. The histological study disclosed extensive mitochondrial impairment in the form of ragged-red fibers or equivalents on oxidative reactions. These findings were associated with an increase in mitochondrial content and a decrease in both mitochondrial respiratory capacity and MRC enzyme activities. Mitochondrial DNA content declined to 53% of control values. Mitochondrial abnormalities had almost disappeared later when the patient became asymptomatic. Our findings support the hypothesis that MRC dysfunction stands at the basis of HAART-related hyperlactatemia.

Kinetics of selective oxidation of lactose to lactobionic acid over Pd-active carbon catalyst

Laktoosi eli maitosokeri on tärkein ainesosa useimpien nisäkkäiden tuottamassa maidossa. Sitä erotetaan herasta, juustosta ja maidosta. Laktoosia käytetään elintarvike- ja lääketeollisuuden raaka-aineena monissaeri tuotteissa. Lääketeollisuudessa laktoosia käytetään esimerkiksi tablettien täyteaineena. Hapettamalla laktoosia voidaan valmistaa laktobionihappoa, 2-keto-laktobionihappoa ja laktuloosia. Laktobionihappoa käytetään biohajoavien pintojen ja kosmetiikkatuotteiden valmistuksessa, sekä sisäelinten säilöntäliuoksissa, joissa laktobionihappo estää happiradikaalien aiheuttamien kudosvaurioiden syntymistä. Tässä työssä laktoosia hapetettiin laktobionihapoksi sekoittimella varustetussa laboratoriomittakaavaisessa panosreaktorissa käyttäenkatalyyttinä palladiumia aktiivihiilellä. Muutamissa kokeissa katalyytin promoottorina käytettiin vismuttia, joka hidastaa katalyytin deaktivoitumista. Työn tarkoituksena oli saada lisää tietoa laktoosin hapettamisen kinetiikasta. Laktoosin hapettumisessa laktobionihapoksi havaittiin selektiivisyyteen vaikuttavan muunmuassa reaktiolämpötila, paine, pH ja käytetyn katalyytin määrä. Katalyyttiä kierrättämällä eri kokeiden välillä saatiin paremmat konversiot, selektiivisyydet ja saannot. Parhaat koetulokset saatiin hapetettaessa synteettisellä ilmalla 60 oC lämpötilassa ja 1 bar paineessa. Tehdyissä kokeissa pH:n säätö tehtiin manuaalisesti, joten pH ei pysynyt koko ajan haluttuna. Laktoosin konversio oli parhaimmillaan 95 %. Laktobionihapon suhteellinen selektiivisyys oli 100% ja suhteellinen saanto 100 %. Kinetiikan matemaattinen mallinnus tehtiin Modest-ohjelmalla käyttäen kokeista saatuja mittaustuloksia.Ohjelman avulla estimoitiin parametreja ja saatiin matemaattinen malli reaktorille. Tässä työssä tehtiin kineettinen mallinnus myös ravistelureaktorissa tehdyille laktoosin hapetuskokeille, missä pH pysyi koko ajan haluttuna 'in-situ' titrauksen avulla. Työn yhteydessä selvitettiin myös mahdollisuutta käyttää monoliittikatalyyttejä laktoosin hapetusreaktiossa.

Developing Service Promise Concept Based on Supply Chain

Diplomityön tavoitteena on analysoida ja kehittää palvelulupauskonseptia toimitusketjuun perustuen Halton Oy:ssä. Työ toteutettiin, koska asiakaslähtöinen liiketoimintatapa on voimakkaasti valtaamassa alaa tuote- ja tuotantopainotteiselta toimintatavalta. Tuotteiden erinomaisuus koetaan markkinoilla yhä useammin itsestään selvyytenä. Prosessien tehokas hallitseminen ja asiakkaan kokeman lisäarvon muodostaminen ovat muodostuneet ratkaisevimmaksi kilpailuedun luojaksi. Toimitusketjun hallinnalla ja sähköisellä kaupankäynnillä on tärkeä rooli tämän kilpailuedun muodostumisessa.Diplomityö käsittelee uuden palvelulupauskonseptin tarjoamia etuja Halton Oy:lle. Työssä pureudutaan toimitusketjun ja sähköisen kaupankäynnin integraatiomahdollisuuksiin. Tarkoituksena on selvittää parhaat mahdolliset kriteerit Haltonin palvelulupauskonseptilleja luoda menetelmät yrityksen materiaalivirtojen sekä uuden konseptin analysoinnille ja kehittämiselle jatkossa.

Monte Carlo Methods in Parameter Estimation of Nonlinear Models

Yksi keskeisimmistä tehtävistä matemaattisten mallien tilastollisessa analyysissä on mallien tuntemattomien parametrien estimointi. Tässä diplomityössä ollaan kiinnostuneita tuntemattomien parametrien jakaumista ja niiden muodostamiseen sopivista numeerisista menetelmistä, etenkin tapauksissa, joissa malli on epälineaarinen parametrien suhteen. Erilaisten numeeristen menetelmien osalta pääpaino on Markovin ketju Monte Carlo -menetelmissä (MCMC). Nämä laskentaintensiiviset menetelmät ovat viime aikoina kasvattaneet suosiotaan lähinnä kasvaneen laskentatehon vuoksi. Sekä Markovin ketjujen että Monte Carlo -simuloinnin teoriaa on esitelty työssä siinä määrin, että menetelmien toimivuus saadaan perusteltua. Viime aikoina kehitetyistä menetelmistä tarkastellaan etenkin adaptiivisia MCMC menetelmiä. Työn lähestymistapa on käytännönläheinen ja erilaisia MCMC -menetelmien toteutukseen liittyviä asioita korostetaan. Työn empiirisessä osuudessa tarkastellaan viiden esimerkkimallin tuntemattomien parametrien jakaumaa käyttäen hyväksi teoriaosassa esitettyjä menetelmiä. Mallit kuvaavat kemiallisia reaktioita ja kuvataan tavallisina differentiaaliyhtälöryhminä. Mallit on kerätty kemisteiltä Lappeenrannan teknillisestä yliopistosta ja Åbo Akademista, Turusta.