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We present a model for mechanical activation of the cardiac tissue depending on the evolution of the transmembrane electrical potential and certain gating/ionic variables that are available in most of electrophysiological descriptions of the cardiac membrane. The basic idea consists in adding to the chosen ionic model one ordinary differential equation for the kinetics of the mechanical activation function. A relevant example illustrates the desired properties of the proposed model, such as delayed muscle contraction and correct magnitude of the muscle fibers' shortening.

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A geophysical and geochemical study has been conducted in a fractured carbonate aquifer located at Combioula in the southwestern Swiss Alps with the objective to detect and characterize hydraulically active fractures along a 260-m-deep borehole. Hydrochemical analyses, borehole diameter, temperature and fluid electrical conductivity logging data were integrated in order to relate electrokinetic self-potential signals to groundwater flow inside the fracture network. The results show a generally good, albeit locally variable correlation of variations of the self-potential signals with variations in temperature, fluid electrical conductivity and borehole diameter. Together with the hydrochemical evidence, which was found to be critical for the interpretation of the self-potential data, these measurements not only made it possible to detect the hydraulically active fractures but also to characterize them as zones of fluid gain or fluid loss. The results complement the available information from the corresponding litholog and illustrate the potential of electrokinetic self-potential signals in conjunction with temperature, fluid electrical conductivity and hydrochemical analyses for the characterization of fractured aquifers, and thus may offer a perspective for an effective quantitative characterization of this increasingly important class of aquifers and geothermal reservoirs.

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In anticipation of regulation involving numeric turbidity limit at highway construction sites, research was done into the most appropriate, affordable methods for surface water monitoring. Measuring sediment concentration in streams may be conducted a number of ways. As part of a project funded by the Iowa Department of Transportation, several testing methods were explored to determine the most affordable, appropriate methods for data collection both in the field and in the lab. The primary purpose of the research was to determine the exchangeability of the acrylic transparency tube for water clarity analysis as compared to the turbidimeter.

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Juvenile dermatomyositis (JDM) is an immune-mediated inflammatory disease affecting the microvasculature of skin and muscle. CD4+CD25+FOXP3+ regulatory T cells (Tregs) are key regulators of immune homeostasis. A role for Tregs in JDM pathogenesis has not yet been established. Here, we explored Treg presence and function in peripheral blood and muscle of JDM patients. We analyzed number, phenotype and function of Tregs in blood from JDM patients by flow cytometry and in vitro suppression assays, in comparison to healthy controls and disease controls (Duchenne's Muscular Dystrophy). Presence of Tregs in muscle was analyzed by immunohistochemistry. Overall, Treg percentages in peripheral blood of JDM patients were similar compared to both control groups. Muscle biopsies of new onset JDM patients showed increased infiltration of numbers of T cells compared to Duchenne's muscular dystrophy. Both in JDM and Duchenne's muscular dystrophy the proportion of FOXP3+ T cells in muscles were increased compared to JDM peripheral blood. Interestingly, JDM is not a self-remitting disease, suggesting that the high proportion of Tregs in inflamed muscle do not suppress inflammation. In line with this, peripheral blood Tregs of active JDM patients were less capable of suppressing effector T cell activation in vitro, compared to Tregs of JDM in clinical remission. These data show a functional impairment of Tregs in a proportion of patients with active disease, and suggest a regulatory role for Tregs in JDM inflammation.

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The study area. located north of Konva (Central Turkey), is composed of Silurian to Cretaceous metamorphosed rocks. The lower unit of the oldest formation (Silurian-Early Permian) is mostly made up of Silurian-Early Carboniferous metacarbonates. These rocks pass laterally and vertically to Devonian-Early Permian series having continental margin, shallow water and pelagic characteristics. They are intruded or juxtaposed to different kinds of metamagmatic rocks. which show MORB. continental arc and within plate characteristics. The Palaeozoic units are covered unconformably by Triassic-Cretaceous metasedimentary units. All these rocks are overthrusted by Mesozoic ophiolites. The Palaeozoic sequence can be seen as a northern Palaeotethys passive, then active margin. The northward subduction of the Palaeotethys ocean during the Carboniferous-Triassic times, induced the development of a magmatic arc and fore-arc sequence (Carboniferous-Permian). Before the Early Triassic (?Late Permian) time. the fore-arc sequence was uplifted above sea level and eroded. The Triassic sequences are regarded as marking the onset of back-arc opening and detachment of the Anatolian Konya block from the active Eurasian margin. Finally. a suture zone formed during the Carman between the Konya region and the Menderes-Tauride Cimmerian block due to the closing of Palaeotethvs. This geodynamic evolution can be correlated with the evolution of the Karaburun sequence in western Turkey.

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The Quaternary Active Faults Database of Iberia (QAFI) is an initiative lead by the Institute of Geology and Mines of Spain (IGME) for building a public repository of scientific data regarding faults having documented activity during the last 2.59 Ma (Quaternary). QAFI also addresses a need to transfer geologic knowledge to practitioners of seismic hazard and risk in Iberia by identifying and characterizing seismogenic fault-sources. QAFI is populated by the information freely provided by more than 40 Earth science researchers, storing to date a total of 262 records. In this article we describe the development and evolution of the database, as well as its internal architecture. Aditionally, a first global analysis of the data is provided with a special focus on length and slip-rate fault parameters. Finally, the database completeness and the internal consistency of the data are discussed. Even though QAFI v.2.0 is the most current resource for calculating fault-related seismic hazard in Iberia, the database is still incomplete and requires further review.

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Methylene blue (MB) and light are used for virus inactivation of plasma for transfusion. However, the presence of MB has been the subject of concern, and efforts have been made to efficiently remove the dye after photo-treatment. For this study, plasma was collected by apheresis from 10 donors (group A), then treated using the MacoPharma THERAFLEX procedure (MB; 1 microM, and light exposure; 180 J/cm(2)) (group B), and finally filtered in order to remove the dye (group C). Proteins were analyzed by two-dimensional electrophoresis, and peptides showing modifications were characterized by mass spectrometry. Clottable and antigenic fibrinogen levels, as well as fibrin polymerization time were measured. Analyses of the gels focused on a region corresponding to pI between 4.5 and 6.5, and M(r) from 7000 to 58 000. In this area, 387 +/- 47 spots matched, and four of these spots presented significant modifications. They corresponded to changes of the gamma-chain of fibrinogen, of transthyretin, and of apolipoprotein A-I, respectively. A decrease of clottable fibrinogen and a prolongation of fibrin polymerization time were observed in groups B and C. Removal of MB by filtration was not responsible for additional protein alterations. The effect of over-treatment of plasma by very high concentrations of MB (50 microM) in association with prolonged light exposure (3 h) was also analyzed, and showed complex alterations of most of the plasma proteins, including fibrinogen gamma-chain, transthyretin, and apolipoprotein A-I. Our data indicates that MB treatment at high concentration and prolonged illumination severely injure plasma proteins. By contrast, at the MB concentration used to inactivate viruses, damages are apparently very restricted.

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OBJECTIVE: We developed interferon-α-kinoid (IFN-K), a drug composed of inactivated IFNα coupled to a carrier protein, keyhole limpet hemocyanin. In human IFNα-transgenic mice, IFN-K induces polyclonal antibodies that neutralize all 13 subtypes of human IFNα. We also previously demonstrated that IFN-K slows disease progression in a mouse model of systemic lupus erythematosus (SLE). This study was undertaken to examine the safety, immunogenicity, and biologic effects of active immunization with IFN-K in patients with SLE. METHODS: We performed a randomized, double-blind, placebo-controlled, phase I/II dose-escalation study comparing 3 or 4 doses of 30 μg, 60 μg, 120 μg, or 240 μg of IFN-K or placebo in 28 women with mild to moderate SLE. RESULTS: IFN-K was well tolerated. Two SLE flares were reported as serious adverse events, one in the placebo group and the other in a patient who concomitantly stopped corticosteroids 2 days after the first IFN-K dose, due to mild fever not related to infection. Transcriptome analysis was used to separate patients at baseline into IFN signature-positive and -negative groups, based on the spontaneous expression of IFN-induced genes. IFN-K induced anti-IFNα antibodies in all immunized patients. Notably, significantly higher anti-IFNα titers were found in signature-positive patients than in signature-negative patients. In IFN signature-positive patients, IFN-K significantly reduced the expression of IFN-induced genes. The decrease in IFN score correlated with the anti-IFNα antibody titer. Serum complement C3 levels were significantly increased in patients with high anti-IFNα antibody titers. CONCLUSION: These results show that IFN-K is well tolerated, immunogenic, and significantly improves disease biomarkers in SLE patients, indicating that further studies of its clinical efficacy are warranted.

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Tämän diplomityön tavoitteena oli testata ja optimoida erään alipainerumpusuodattimen toimivuutta, ja lisäksi maksimoida tuottavuus ja vertailla erilaisten pesumenetelmientehokkuutta. Testilietteiden ¿ rautarikasteen ja täyteainepastan ¿ karakterisointi oli myös tärkeää. Kirjallisuusosassa tarkasteltiin lyhyesti neste-kiintoaine-erotuksen teoriaa, erityisesti alipainesuodatusta ja alipainerumpusuodattimia. Lisäksi käsiteltiin kapillaarisuodatuksen toimintaperiaatteita sekä selvitettiin kaivosteollisuuden veden talteenottokeinoja, kiintoainejäämien käsittelymenetelmiä ja Chilen kaivosteollisuuden nykytilaa. Työn kokeellinen osa suoritettiin käyttämällä raskaita ja kiintoainepitoisuuksiltaan korkeita lietteitä, eli rautarikastetta ja täyteainepastaa. Kokeet suoritettiin erityisellä alipainerumpusuodattimella, joka oli muokattu perinteisestäpäältä syötettävästä alipainerumpusuodattimesta. Kokeissa tutkittiin pyörimisnopeuden ja erilaisten pesumenetelmien vaikutusta kakun kosteuteen ja suodatuskapasiteettiin. Koelietteiden karakterisointi suoritettiin analysoimalla partikkelikokojakauma, kiintoainepitoisuus, metallipitoisuus ja koostumus. Kokeiden perusteella havaittiin, että rummun pyörimisnopeudella ja lietteen kiintoainepitoisuudella on merkittävä vaikutus suodatuskapasiteettiin ja kakun kosteuspitoisuuteen. Havaittiin myös, että kakun kosteuspitoisuuksissa ja rummun suodatuskapasiteeteissa oli eroja, kun verrattiin eri suodatinväliaineen pesumenetelmiä. Täten oikean pesumenetelmän valinta on tärkeää, ja sillä pystytään lisäämään suodatinväliaineen käyttöikää.

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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.

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Chemokines constitute an expanding protein family of over 40 members which exhibit a wide variety of biological activities and are involved in many normal physiological processes, such as cellular migration, differentiation and activation, but also in pathological situations, such as inflammation and metastasis. Over the last few years, we have developed methods to manufacture long synthetic peptides of up to 130 residues, and to achieve the formation of native-like cysteine pairings. This ability prompted us to undertake the total chemical synthesis of chemokines. So far, we have successfully produced over 30 chemokine species, which exhibit biological activities similar to, or greater than, those reported by others. Chemical synthesis offers a clear advantage over recombinant technologies for the introduction of fluorochromes and haptens at molecularly defined positions. In addition, approval of chemically synthesized products for use in humans is straightforward compared with material produced by biological methods.

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Purpose: To evaluate the reproducibility of Cirrus-SD OCT measurements and to compare central macular thickness (CMT) measurements between TD-Stratus and SD-Cirrus OCT in patients with active exudative AMD. Methods: Consecutive case series of patients with active exudative AMD seen in the Medical Retina Department. Patients underwent 1 scan with Stratus (macular thickness map protocol) and 5 scans with Cirrus (Macular Cube protocol) at the same visit by the same experienced examiner. To be included, patients best-corrected visual acuity (BCVA) had to be >20/200 while all scans had to be of sufficient quality, well-centered and at least one Cirrus scan with CMT >300 microns. The repeatability of the SD Cirrus was estimated by using all 5 CMT measurements and the mean of the Cirrus measurements was compared with the CMT obtained by TD Stratus. Results: Cirrus OCT demonstrated high intraobserver repeatability at the central foveal region (ICC 96%). The mean of the CMT measurements was 321microns for Stratus and 387 microns for Cirrus. The average difference was 65m (SD=30). The coefficient of concordance between Stratus and Cirrus CMT measurements was rho=0,749 with a high precision and a moderate accuracy. The equation of the line of regression between Stratus and meanCirrus is given by the following: M_stratus = 0,848 x m_cirrus - 4,496 (1).Conclusions: The Cirrus macular cube protocol allows reproducible CMT measurements in patients with active exudative AMD. In cases of upgrading from TD to SD use and vice versa, there is the possibility to predict the measurements by using the equation (1). These real life data and conclusions can help in improving our clinical management of patients with neovascular AMD.