Sm14 gene expression in different stages of the Schistosoma mansoni life cycle and immunolocalization of the Sm14 protein within the adult worm

Sm14 is a 14-kDa vaccine candidate antigen from Schistosoma mansoni that seems to be involved in cytoplasmic trafficking of fatty acids. Although schistosomes have a high requirement for lipids, they are not able to synthesize fatty acids and sterols de novo. Thus, they must acquire host lipids. In order to determine whether Sm14 is present in different stages of the life cycle of the parasite, we performed RT-PCR. Sm14 mRNA was identified in all stages of the life cycle studied, mainly schistosomulum, adult worm and egg. Additionally, we used a rabbit anti-Sm14 polyclonal antibody in an indirect immunofluorescence assay to localize Sm14 in adult worm sections. The basal lamella of the tegument and the gut epithelium were strongly labeled. These tissues have a high flow of and demand for lipids, a finding that supports the putative role of Sm14 as an intracellular transporter of fatty acids from host cells.

Evaluating land-use related environmental impacts of biomass value chains for decision-support : Comparison and testing of methodologies proposed for environmental life cycle assessment

Life cycle assessment (LCA) is one of the most established quantitative tools for environmental impact assessment of products. To be able to provide support to environmentally-aware decision makers on environmental impacts of biomass value-chains, the scope of LCA methodology needs to be augmented to cover landuse related environmental impacts. This dissertation focuses on analysing and discussing potential impact assessment methods, conceptual models and environmental indicators that have been proposed to be implemented into the LCA framework for impacts of land use. The applicability of proposed indicators and impact assessment frameworks is tested from practitioners' perspective, especially focusing on forest biomass value chains. The impacts of land use on biodiversity, resource depletion, climate change and other ecosystem services is analysed and discussed and the interplay in between value choices in LCA modelling and the decision-making situations to be supported is critically discussed. It was found out that land use impact indicators are necessary in LCA in highlighting differences in impacts from distinct land use classes. However, many open questions remain on certainty of highlighting actual impacts of land use, especially regarding impacts of managed forest land use on biodiversity and ecosystem services such as water regulation and purification. The climate impact of energy use of boreal stemwood was found to be higher in the short term and lower in the long-term in comparison with fossil fuels that emit identical amount of CO2 in combustion, due to changes implied to forest C stocks. The climate impacts of energy use of boreal stemwood were found to be higher than the previous estimates suggest on forest residues and stumps. The product lifetime was found to have much higher influence on the climate impacts of woodbased value chains than the origin of stemwood either from thinnings or final fellings. Climate neutrality seems to be likely only in the case when almost all the carbon of harvested wood is stored in long-lived wooden products. In the current form, the land use impacts cannot be modelled with a high degree of certainty nor communicated with adequate level of clarity to decision makers. The academia needs to keep on improving the modelling framework, and more importantly, clearly communicate to decision-makers the limited certainty on whether land-use intensive activities can help in meeting the strict mitigation targets we are globally facing.

Interruption of the blood-stage cycle of the malaria parasite, Plasmodium chabaudi, by protein tyrosine kinase inhibitors

Malaria is a devastating disease caused by a unicellular protozoan, Plasmodium, which affects 3.7 million people every year. Resistance of the parasite to classical treatments such as chloroquine requires the development of new drugs. To gain insight into the mechanisms that control Plasmodium cell cycle, we have examined the effects of kinase inhibitors on the blood-stage cycle of the rodent malaria parasite, Plasmodium chabaudi. In vitro incubation of red blood cells for 17 h at 37ºC with the inhibitors led to a decrease in the percent of infected cells, compared to control treatment, as follows: genistein (200 µM - 75%), staurosporine (1 µM - 58%), R03 (1 µM - 75%), and tyrphostins B44 (100 µM - 66%) and B46 (100 µM - 68%). All these treatments were shown to retard or prevent maturation of the intraerythrocytic parasites. The diverse concentration ranges at which these inhibitors exert their effects give a clue as to the types of signals that initiate the transitions between the different developmental stages of the parasite. The present data support our hypothesis that the maturation of the intraerythrocytic cycle of malaria parasites requires phosphorylation. In this respect, we have recently reported a high Ca2+ microenvironment surrounding the parasite within red blood cells. Several kinase activities are modulated by Ca2+. The molecular identification of the targets of these kinases could provide new strategies against malaria.

Supply base development for life-cycle business

Yritysten liiketoimintamallit ovat jatkuvan kehityksen kohteena. Viimeisinä vuosina valmistavien yhtiöiden kiinnostus huolehtia asiakkaistaan koko tuotteen elinkaaren aikana ja tarjota erilaisia palveluita asiakkailleen on kasvanut. Tämän palvelujen laajentumisen myötä myös vaateet yrityksen omaa toimittajakenttää kohtaan ovat muuttuneet. Yritykset eivät kykene tuottamaan kaikkia tuotteistamiaan palveluja itse, jolloin yrityksen toimittajakenttä ja sen kyvykkyydet tuottaa tarvittavia palveluita ovat avainasemassa yrityksen menestystekijänä. Tämän työn teoriaosuudessa on esitelty toimittajakentän hallinnan perusteorioita. Kirjallisuus osuuden lisäksi työssä on hyödynnetty toimintatutkimusta kohdeyrityksessä. Tässä diplomityössä on tutkittu mahdollisia keinoja kehittää organisaation omaa toimintaa ja sekä yrityksen toimittajakenttää niin, että se tukee liiketoimintamallin kehitystä koneenrakennusyrityksestä kohti elinkaariliiketoimintaa. Työssä esitetyt keinot voidaan ottaa käyttöön, joko yksitellen tai kokonaisuutena.

Novel virtual environment and real-time simulation based methods for improving life-cycle efficiency of non-road mobile machinery

Virtual environments and real-time simulators (VERS) are becoming more and more important tools in research and development (R&D) process of non-road mobile machinery (NRMM). The virtual prototyping techniques enable faster and more cost-efficient development of machines compared to use of real life prototypes. High energy efficiency has become an important topic in the world of NRMM because of environmental and economic demands. The objective of this thesis is to develop VERS based methods for research and development of NRMM. A process using VERS for assessing effects of human operators on the life-cycle efficiency of NRMM was developed. Human in the loop simulations are ran using an underground mining loader to study the developed process. The simulations were ran in the virtual environment of the Laboratory of Intelligent Machines of Lappeenranta University of Technology. A physically adequate real-time simulation model of NRMM was shown to be reliable and cost effective in testing of hardware components by the means of hardware-in-the-loop (HIL) simulations. A control interface connecting integrated electro-hydraulic energy converter (IEHEC) with virtual simulation model of log crane was developed. IEHEC consists of a hydraulic pump-motor and an integrated electrical permanent magnet synchronous motorgenerator. The results show that state of the art real-time NRMM simulators are capable to solve factors related to energy consumption and productivity of the NRMM. A significant variation between the test drivers is found. The results show that VERS can be used for assessing human effects on the life-cycle efficiency of NRMM. HIL simulation responses compared to that achieved with conventional simulation method demonstrate the advances and drawbacks of various possible interfaces between the simulator and hardware part of the system under study. Novel ideas for arranging the interface are successfully tested and compared with the more traditional one. The proposed process for assessing the effects of operators on the life-cycle efficiency will be applied for wider group of operators in the future. Driving styles of the operators can be analysed statistically from sufficient large result data. The statistical analysis can find the most life-cycle efficient driving style for the specific environment and machinery. The proposed control interface for HIL simulation need to be further studied. The robustness and the adaptation of the interface in different situations must be verified. The future work will also include studying the suitability of the IEHEC for different working machines using the proposed HIL simulation method.

NFAT transcription factors: from cell cycle to tumor development

The nuclear factor of activated T cells (NFAT) family of transcription factors has been primarily identified in immune cells; however, these proteins have been recently found to be functionally active in several other non-immune cell types. NFAT proteins are activated upon different stimuli that lead to increased intracellular calcium levels. Regardless of their widely known cytokine gene expression properties, NFATs have been shown to regulate other genes related to cell cycle progression, cell differentiation and apoptosis, revealing a broader role for these proteins in normal cell physiology. Several reports have addressed the participation of NFATs in many aspects of malignant cell transformation and tumorigenic processes. In this review, we will discuss the involvement of the different NFAT family members in the regulation of cell cycling, differentiation and tumor formation, and also its implications on oncogenesis. Better understanding the mechanisms by which NFATs regulate cell cycle and tumor-related events should be relevant for the development of rational anti-cancer therapies.

Effects of gamma-radiation on cell growth, cycle arrest, death, and superoxide dismutase expression by DU 145 human prostate cancer cells

Gamma-irradiation (gamma-IR) is extensively used in the treatment of hormone-resistant prostate carcinoma. The objective of the present study was to investigate the effects of 60Co gamma-IR on the growth, cell cycle arrest and cell death of the human prostate cancer cell line DU 145. The viability of DU 145 cells was measured by the Trypan blue exclusion assay and the 3(4,5-dimethylthiazol-2-yl)-2,5,diphenyltetrazolium bromide test. Bromodeoxyuridine incorporation was used for the determination of cell proliferation. Cell cycle arrest and cell death were analyzed by flow cytometry. Superoxide dismutase (SOD), specifically CuZnSOD and MnSOD protein expression, after 10 Gy gamma-IR, was determined by Western immunoblotting analysis. gamma-IR treatment had a significant (P < 0.001) antiproliferative and cytotoxic effect on DU 145 cells. Both effects were time and dose dependent. Also, the dose of gamma-IR which inhibited DNA synthesis and cell proliferation by 50% was 9.7 Gy. Furthermore, gamma-IR induced cell cycle arrest in the G2/M phase and the percentage of cells in the G2/M phase was increased from 15% (control) to 49% (IR cells), with a nonsignificant induction of apoptosis. Treatment with 10 Gy gamma-IR for 24, 48, and 72 h stimulated CuZnSOD and MnSOD protein expression in a time-dependent manner, approximately by 3- to 3.5-fold. These data suggest that CuZnSOD and MnSOD enzymes may play an important role in the gamma-IR-induced changes in DU 145 cell growth, cell cycle arrest and cell death.

Design and Drive-Cycle Based Analysis of Direct-Driven Permanent Magnet Synchronous Machine for a Small Urban Use Electric Vehicle

A direct-driven permanent magnet synchronous machine for a small urban use electric vehicle is presented. The measured performance of the machine at the test bench as well as the performance over the modified New European Drive Cycle will be given. The effect of optimal current components, maximizing the efficiency and taking into account the iron loss, is compared with the simple id=0 – control. The machine currents and losses during the drive cycle are calculated and compared with each other.

Luteal phase of the menstrual cycle increases sweating rate during exercise

The present study evaluated whether the luteal phase elevation of body temperature would be offset during exercise by increased sweating, when women are normally hydrated. Eleven women performed 60 min of cycling exercise at 60% of their maximal work load at 32ºC and 80% relative air humidity. Each subject participated in two identical experimental sessions: one during the follicular phase (between days 5 and 8) and the other during the luteal phase (between days 22 and 25). Women with serum progesterone >3 ng/mL, in the luteal phase were classified as group 1 (N = 4), whereas the others were classified as group 2 (N = 7). Post-exercise urine volume (213 ± 80 vs 309 ± 113 mL) and specific urine gravity (1.008 ± 0.003 vs 1.006 ± 0.002) changed (P < 0.05) during the luteal phase compared to the follicular phase in group 1. No menstrual cycle dependence was observed for these parameters in group 2. Sweat rate was higher (P < 0.05) in the luteal (3.10 ± 0.81 g m-2 min-1) than in the follicular phase (2.80 ± 0.64 g m-2 min-1) only in group 1. During exercise, no differences related to menstrual cycle phases were seen in rectal temperature, heart rate, rate of perceived exertion, mean skin temperature, and pre- and post-exercise body weight. Women exercising in a warm and humid environment with water intake seem to be able to adapt to the luteal phase increase of basal body temperature through reduced urinary volume and increased sweating rate.

Long-term loss of color vision after exposure to mercury vapor

We evaluated the color vision of 24 subjects (41.6 ± 6.5 years; 6 females) who worked in fluorescent lamp industries. They had been occupationally exposed to mercury vapor (10.6 ± 5.2 years) and had been away from the source of exposure for 6.4 ± 4.04 years. Mean urinary concentration of mercury was 40.6 ± 36.4 µg/g creatinine during or up to 1 year after exposure and 2.71 ± 1.19 µg/g creatinine at the time of color vision testing or up to 1 year thereafter. All patients were diagnosed with chronic mercury intoxication, characterized by clinical symptoms and neuropsychological alterations. A control group (N = 36, 48.6 ± 11.9 years, 10 females, 1.5 ± 0.47 µg mercury/g creatinine) was subjected to the same tests. Inclusion criteria for both groups were Snellen VA 20/30 or better and absence of known ophthalmologic pathologies. Color discrimination was assessed with the Farnsworth D-15 test (D-15) and with the Lanthony D-15d test (D-15d). Significant differences were found between the two eyes of the patients (P < 0.001) in both tests. Results for the worst eye were also different from controls for both tests: P = 0.014 for D-15 and P < 0.001 for D-15d. As shown in previous studies, the D-15d proved to be more sensitive than the D-15 for the screening and diagnosis of the color discrimination losses. Since color discrimination losses were still present many years after the end of exposure, they may be considered to be irreversible, at least under the conditions of the present study.

Effects of life cycle profits on the profitability of industrial heavy duty cranes

The goal of the thesis was to investigate how much after-sales profits a crane sale generates over the life cycle of the crane and the effects of these after-sales profits on the overall profitability of the crane. The thesis utilizes theories about life cycle costing from an equipment and service supplier’s point of view. However, instead of costs, the thesis is focused on the life cycle after-sales profits from maintenance services and spare parts provided for the sold crane. The case study approach was chosen and a total of five cranes from three different segments were investigated. An eight-step life cycle profit calculation model was developed in order to analyze the chosen cases’ life cycle profits systematically. The results of the investigation suggest that the life cycle after-sales profits are significant in value. In the case analyses they accounted for between 20% and 44% of the overall life cycle profits of the case cranes. The after-sales profits should be taken into account already in the pricing when offering a crane to a customer.

Effects of pentoxifylline treatment before freezing on motility, viability and acrosome status of poor quality human spermatozoa cryopreserved by the liquid nitrogen vapor method

The objective of the present study was to investigate the effects of the direct addition of pentoxifylline (PF) to the ejaculates of men with poor sperm quality before freezing on post-thaw sperm motility, viability, acrosome integrity, and agonist-induced acrosome reaction. Semen specimens from 16 infertile men with impaired sperm count and motility (oligoasthenozoospermia) were divided into two equal aliquots: one received no treatment (control) while the other was incubated with 5 mM PF (treated). Both aliquots were cryopreserved by the liquid nitrogen vapor method. Motility was assessed according to WHO criteria. Acrosome integrity and spontaneous and calcium ionophore-induced acrosome reactions were assessed with fluorescein isothiocyanate-conjugated peanut agglutinin combined with a supra-vital dye (Hoechst-33258). Cryopreservation impaired sperm motility (percentage reduction: 87.4 (interquartile range, IQ: 70.3-92.9) vs 89.1 (IQ: 72.7-96.0%)), viability (25.9 (IQ: 22.2-29.7) vs 25.6 (IQ: 19.7-40.3%)) and acrosome integrity (18.9 (IQ: 5.4-38.9) vs 26.8 (IQ: 0.0-45.2%)) to the same extent in both treated and control aliquots. However, PF treatment before freezing improved the acrosome reaction to ionophore challenge test scores in cryopreserved spermatozoa (9.7 (IQ: 6.6-19.7) vs 4.8 (IQ: 0.5-6.8%); P = 0.002). These data show that pre-freeze treatment of poor quality human sperm with pentoxifylline did not improve post-thaw motility or viability nor did it prevent acrosomal loss during the freeze-thaw process. However, PF, as used, improved the ability of thawed spermatozoa to undergo the acrosome reaction in response to calcium ionophore. The present data indicate that treatment of poor quality human sperm with PF may enhance post-thaw sperm fertilizing ability.

Neuropsychological dysfunction related to earlier occupational exposure to mercury vapor

We assessed the neuropsychological test performances of 26 patients (mean age = 41.5 ± 6.1 years; mean years of education = 9.8 ± 1.8; 20 males) diagnosed with chronic occupational mercurialism who were former workers at a fluorescent lamp factory. They had been exposed to elemental mercury for an average of 10.2 ± 3.8 years and had been away from this work for 6 ± 4.7 years. Mean urinary mercury concentrations 1 year after cessation of work were 1.8 ± 0.9 µg/g creatinine. Twenty control subjects matched for age, gender, and education (18 males) were used for comparison. Neuropsychological assessment included attention, inhibitory control, verbal and visual memory, verbal fluency, manual dexterity, visual-spatial function, executive function, and semantic knowledge tests. The Beck Depression Inventory and the State and Trait Inventory were used to assess depression and anxiety symptoms, respectively. The raw score for the group exposed to mercury indicated slower information processing speed, inferior performance in psychomotor speed, verbal spontaneous recall memory, and manual dexterity of the dominant hand and non-dominant hand (P < 0.05). In addition, the patients showed increased depression and anxiety symptoms (P < 0.001). A statistically significant correlation (Pearson) was demonstrable between mean urinary mercury and anxiety trait (r = 0.75, P = 0.03). The neuropsychological performances of the former workers suggest that occupational exposure to elemental mercury has long-term effects on information processing and psychomotor function, with increased depression and anxiety also possibly reflecting the psychosocial context.

Protein-energy malnutrition halts hemopoietic progenitor cells in the G0/G1 cell cycle stage, thereby altering cell production rates

Protein energy malnutrition (PEM) is a syndrome that often results in immunodeficiency coupled with pancytopenia. Hemopoietic tissue requires a high nutrient supply and the proliferation, differentiation and maturation of cells occur in a constant and balanced manner, sensitive to the demands of specific cell lineages and dependent on the stem cell population. In the present study, we evaluated the effect of PEM on some aspects of hemopoiesis, analyzing the cell cycle of bone marrow cells and the percentage of progenitor cells in the bone marrow. Two-month-old male Swiss mice (N = 7-9 per group) were submitted to PEM with a low-protein diet (4%) or were fed a control diet (20% protein) ad libitum. When the experimental group had lost about 20% of their original body weight after 14 days, we collected blood and bone marrow cells to determine the percentage of progenitor cells and the number of cells in each phase of the cell cycle. Animals of both groups were stimulated with 5-fluorouracil. Blood analysis, bone marrow cell composition and cell cycle evaluation was performed after 10 days. Malnourished animals presented anemia, reticulocytopenia and leukopenia. Their bone marrow was hypocellular and depleted of progenitor cells. Malnourished animals also presented more cells than normal in phases G0 and G1 of the cell cycle. Thus, we conclude that PEM leads to the depletion of progenitor hemopoietic populations and changes in cellular development. We suggest that these changes are some of the primary causes of pancytopenia in cases of PEM.

Radioiodine plus recombinant human thyrotropin do not cause acute airway compression and are effective in reducing multinodular goiter

Recombinant human thyrotropin (rhTSH) reduces the activity of radioiodine required to treat multinodular goiter (MNG), but acute airway compression can be a life-threatening complication. In this prospective, randomized, double-blind, placebo-controlled study, we assessed the efficacy and safety (including airway compression) of different doses of rhTSH associated with a fixed activity of 131I for treating MNG. Euthyroid patients with MNG (69.3 ± 62.0 mL, 20 females, 2 males, 64 ± 7 years) received 0.1 mg (group I, N = 8) or 0.01 mg (group II, N = 6) rhTSH or placebo (group III, N = 8), 24 h before 1.11 GBq 131I. Radioactive iodine uptake was determined at baseline and 24 h after rhTSH and thyroid volume (TV, baseline and 6 and 12 months after treatment) and tracheal cross-sectional area (TCA, baseline and 2, 7, 180, and 360 days after rhTSH) were determined by magnetic resonance; antithyroid antibodies and thyroid hormones were determined at frequent intervals. After 6 months, TV decreased significantly in groups I (28.5 ± 17.6%) and II (21.6 ± 17.8%), but not in group III (2.7 ± 15.3%). After 12 months, TV decreased significantly in groups I (36.7 ± 18.1%) and II (37.4 ± 27.1%), but not in group III (19.0 ± 24.3%). No significant changes in TCA were observed. T3 and free T4 increased transiently during the first month. After 12 months, 7 patients were hypothyroid (N = 3 in group I and N = 2 in groups II and III). rhTSH plus a 1.11-GBq fixed 131I activity did not cause acute or chronic changes in TCA. After 6 and 12 months, TV reduction was more pronounced among patients treated with rhTSH plus 131I.