Clinical pharmacokinetics of mycophenolic acid and its metabolites in solid organ transplant recipient

Mycophenolate mofetil (MMF), an ester prodrug of the immunosuppressant mycophenolic acid (MPA), is widely used for maintenance immunosuppressive therapy and prevention of renal allograft rejection in renal transplant recipients.MPA inhibits inosine monophosphate dehydrogenase (IMPDH), an enzyme involved in the “de novo” synthesis of purine nucleotides, thus suppressing both T-cell and B-cell proliferation. MPA shows a complex pharmacokinetics with considerable interand intra- patient by between- and within patient variabilities associated to MPA exposure. Several factors may contribute to it. The pharmacokinetic modeling according to the population pharmacokinetic approach with the non-linear mixed effects models has shown to be a powerful tool to describe the relationships between MMF doses and the MPA exposures and also to identify potential predictive patients’ demographic and clinical characteristics for dose tailoring during the post-transplant immunosuppresive treatment.

Clinical pharmacokinetics of mycophenolic acid and its metabolites in solid organ transplant recipient

Mycophenolate mofetil (MMF), an ester prodrug of the immunosuppressant mycophenolic acid (MPA), is widely used for maintenance immunosuppressive therapy and prevention of renal allograft rejection in renal transplant recipients.MPA inhibits inosine monophosphate dehydrogenase (IMPDH), an enzyme involved in the “de novo” synthesis of purine nucleotides, thus suppressing both T-cell and B-cell proliferation. MPA shows a complex pharmacokinetics with considerable interand intra- patient by between- and within patient variabilities associated to MPA exposure. Several factors may contribute to it. The pharmacokinetic modeling according to the population pharmacokinetic approach with the non-linear mixed effects models has shown to be a powerful tool to describe the relationships between MMF doses and the MPA exposures and also to identify potential predictive patients’ demographic and clinical characteristics for dose tailoring during the post-transplant immunosuppresive treatment.

Cell-mediated immunity to predict cytomegalovirus disease in high-risk solid organ transplant recipients.

Late-onset cytomegalovirus (CMV) disease commonly occurs after discontinuation of antiviral prophylaxis. We determined the utility of testing CD8+ T-cell response against CMV as a predictor of late-onset CMV disease after a standard course of antiviral prophylaxis. Transplant patients at high-risk for CMV disease were enrolled. CD8+ T-cell-mediated immunity (CMI) was tested using the QuantiFERON-CMV assay at baseline, 1, 2 and 3 months posttransplant by measurement of interferon-gamma response to whole blood stimulation with a 21-peptide pool. The primary outcome was the ability of CMI testing to predict CMV disease in the first 6 months posttransplant. There were 108 evaluable patients (D+/R+ n = 39; D-/R+ n = 34; D+/R- n = 35) of whom 18 (16.7%) developed symptomatic CMV disease. At the end of prophylaxis, CMI was detectable in 38/108 (35.2%) patients (cutoff 0.1 IU/mL interferon-gamma). CMV disease occurred in 2/38 (5.3%) patients with a detectable interferon-gamma response versus 16/70 (22.9%) patients with a negative response; p = 0.038. In the subgroup of D+/R- patients, CMV disease occurred in 1/10 (10.0%) patients with a detectable interferon-gamma response (cutoff 0.1 IU/mL) versus 10/25 (40.0%) patients with a negative CMI, p = 0.12. Monitoring of CMI may be useful for predicting late-onset CMV disease.

Maximum likelihood Linear Programming Data Fusion for Speaker Recognition

Biometric system performance can be improved by means of data fusion. Several kinds of information can be fused in order to obtain a more accurate classification (identification or verification) of an input sample. In this paper we present a method for computing the weights in a weighted sum fusion for score combinations, by means of a likelihood model. The maximum likelihood estimation is set as a linear programming problem. The scores are derived from a GMM classifier working on a different feature extractor. Our experimental results assesed the robustness of the system in front a changes on time (different sessions) and robustness in front a change of microphone. The improvements obtained were significantly better (error bars of two standard deviations) than a uniform weighted sum or a uniform weighted product or the best single classifier. The proposed method scales computationaly with the number of scores to be fussioned as the simplex method for linear programming.

Performance Characteristics of an Axial-Flux Solid-Rotor-Core Induction Motor

The integration of electric motors and industrial appliances such as pumps, fans, and compressors is rapidly increasing. For instance, the integration of an electric motor and a centrifugal pump provides cost savings and improved performance characteristics. Material cost savings are achieved when an electric motor is integrated into the shaft of a centrifugal pump, and the motor utilizes the bearings of the pump. This arrangement leads to a smaller configuration that occupies less floor space. The performance characteristics of a pump drive can be improved by using the variable-speed technology. This enables the full speed control of the drive and the absence of a mechanical gearbox and couplers. When using rotational speeds higher than those that can be directly achieved by the network frequency the structure of the rotor has to be mechanically durable. In this thesis the performance characteristics of an axial-flux solid-rotor-core induction motor are determined. The motor studied is a one-rotor-one-stator axial-flux induction motor, and thus, there is only one air-gap between the rotor and the stator. The motor was designed for higher rotational speeds, and therefore a good mechanical strength of the solid-rotor-core rotor is required to withstand the mechanical stresses. The construction of the rotor and the high rotational speeds together produce a feature, which is not typical of traditional induction motors: the dominating loss component of the motor is the rotor eddy current loss. In the case of a typical industrial induction motor instead the dominating loss component is the stator copper loss. In this thesis, several methods to decrease the rotor eddy current losses in the case of axial-flux induction motors are presented. A prototype motor with 45 kW output power at 6000 min-1 was designed and constructed for ascertaining the results obtained from the numerical FEM calculations. In general, this thesis concentrates on the methods for improving the electromagnetic properties of an axial-flux solid-rotor-core induction motor and examines the methods for decreasing the harmonic eddy currents of the rotor. The target is to improve the efficiency of the motor and to reach the efficiency standard of the present-day industrial induction motors equipped with laminated rotors.

Aerodynamical instability of web

Diplomityön tavoitteena oli tutkia miten ilman turbulenttisuus vaikuttaa tasaisesti liikkuvan rainan tilaan. Yhtenä sovelluskohteena teollisuudessa voidaan mainita esimerkiksi leiju-kuivain. Tiedetään, että konenopeuksien kasvu ja siitä johtuva ilmavirran nopeuden kasvu aiheuttaa voimavaikutuksia rainaan ja voi aiheuttaa lepatusta. Lepatus johtaa dynaamiseen epästabiilisuuteen, joka voidaan havaita, kun lineaarinen systeemi tulee epävakaaksi ja joh-taa epälineaariseen, rajoitettuun värähtelyyn. Lepatus huonontaa tuotteiden laatua ja voi johtaa ratakatkoihin. Työssä on esitetty tietoa ilman ja rainan vuorovaikutuksesta, jota hyödyntämällä voidaan kehittää yksinkertaistettu malli, jonka avulla liikkuvaa rainaa voidaan simuloida kuivaimes-sa. Kaasufaasin virtausyhtälöt on ratkaistu eri turbulenttimalleja käyttäen. Myös viskoelas-tisen rainan muodonmuutosta on tarkasteltu. Koska rainalle ei ole kirjallisuudesta saatavilla tarkkoja fysikaalisia ja mekaanisia arvoja, näitä ominaisuuksia testattiin eri arvoilla, jotta rainan käyttäytymistä jännityksen alaisena voidaan tarkastella. Näiden ominaisuuksien tun-teminen on ensiarvoisen tärkeää määritettäessä rainan aeroviskoelastista käyttäytymistä. Virtaussimulointi on kallista ja aikaa vievää. Tämä tarkoittaa uusien tutkimusmenetelmien omaksumista. Tässä työssä vaihtoehtoisena lähestymistapana on esitetty yksinkertaistettu malli, joka sisältää ilman ja rainan vuorovaikutusta kuvaavat ominaisuudet. Mallin avulla saadaan tietoa epälineaarisuuden ja turbulenssin vaikutuksesta sekä monimutkaisesta yh-teydestä stabiilisuuden ja ulkoisesti aikaansaadun värähtelyn sekä itse aiheutetun värähtelyn välillä. Työn lopussa on esitetty havainnollinen esimerkki, jolla voidaan kuvata olosuhteita, jossa rainan tasainen liike muuttuu epävakaaksi. Kun turbulenttisuudesta johtuva painevaih-telu ylittää tietyn rajan, rainan värähtely kasvaa muuttuen satunnaisesta järjestäytyneeksi. Saaduttulokset osoittavat, että turbulenttisuudella on suuri vaikutus eikä sitä voi jättää huomioimatta. Myös rainan viskoelastiset ominaisuudet tulee huomioida, jotta rainan käyt-täytymistä voidaan kuvata tarkasti.

The high-speed induction motor: calculating the effects of solid-rotor material on machine characteristics

A method for the analysis of high-speed solid-rotor induction motors in presented. The analysis is based on a new combination of the three dimensional linear method and the transfer matrix method. Both saturation and finite length effects are taken into account. The active region of the solid rotor is divided into saturated and unsaturated parts. The time dependence is assumed to be sinusoidal and phasor quantities are used in the solution. The method is applied to the calculation of smooth solid rotors manufactured of different materials. Six rotor materials are tested: three construction steels, pure iron, a cobaltiron alloy and an aluminium alloy. The results obtained by the method agree fairly well with the measurement quantities.

High-Speed Solid-Rotor Induction Machine – Electromagnetic Calculation and Design

Within the latest decade high-speed motor technology has been increasingly commonly applied within the range of medium and large power. More particularly, applications like such involved with gas movement and compression seem to be the most important area in which high-speed machines are used. In manufacturing the induction motor rotor core of one single piece of steel it is possible to achieve an extremely rigid rotor construction for the high-speed motor. In a mechanical sense, the solid rotor may be the best possible rotor construction. Unfortunately, the electromagnetic properties of a solid rotor are poorer than the properties of the traditional laminated rotor of an induction motor. This thesis analyses methods for improving the electromagnetic properties of a solid-rotor induction machine. The slip of the solid rotor is reduced notably if the solid rotor is axially slitted. The slitting patterns of the solid rotor are examined. It is shown how the slitting parameters affect the produced torque. Methods for decreasing the harmonic eddy currents on the surface of the rotor are also examined. The motivation for this is to improve the efficiency of the motor to reach the efficiency standard of a laminated rotor induction motor. To carry out these research tasks the finite element analysis is used. An analytical calculation of solid rotors based on the multi-layer transfer-matrix method is developed especially for the calculation of axially slitted solid rotors equipped with wellconducting end rings. The calculation results are verified by using the finite element analysis and laboratory measurements. The prototype motors of 250 – 300 kW and 140 Hz were tested to verify the results. Utilization factor data are given for several other prototypes the largest of which delivers 1000 kW at 12000 min-1.

GdBaCo2O5+x layered perovskite as an intermediate temperature solid oxide fuel cell cathode

GdBaCo2O5+x (GBCO) was evaluated as a cathode for intermediate-temperature solid oxide fuel cells. A porous layer of GBCO was deposited on an anode-supported fuel cell consisting of a 15m thick electrolyte of yttria-stabilized zirconia (YSZ) prepared by dense screen-printing anda Ni–YSZ cermet as an anode (Ni–YSZ/YSZ/GBCO). Values of power density of 150 mW cm−2 at 700◦C and ca. 250 mW cm−2 at 800◦C are reported for this standard configuration using 5% of H2 in nitrogen as fuel. An intermediate porous layer of YSZ was introduced between the electrolyte and the cathode improving the performance of the cell. Values for power density of 300 mW cm−2 at 700◦C and ca. 500 mW cm−2 at 800◦C in this configuration were achieved.

Determinação turbidimétrica de dipirona em fluxo utilizando um reator contendo cloreto de prata imobilizado em resina poliéster

A simple flow injection procedure was developed for determining dipyrone (1-phenyl-2,3-dimethyl-4-methylaminomethano-5-pyrazolone sodium, metamizol, analgin) in pharmaceutical formulations. The determination is based on the reduction of Ag+ ions to Ag0 by dipyrone. A colloidal suspension of Ag0 produced was transported by carrier solution (0.01 mol L-1 NaOH) and turbidimetrically detected at 425 nm. The analytical curve for dipyrone was linear in the range from 5.0 x 10-4 to 2.5 x 10-3 mol L-1 with a correlation coefficient of 0.9990. The detection limit was 1.3 x 10-4 mol L-1 (3sigmaB/slope). The relative standard deviation for ten successive measurements was 1.8% and an analytical frequency of 45 h-1 was obtained. The recovery values from three samples ranged from 96.0 to 102%.

Un método de bajo costo para la determinación de cobre a nivel de vestigios en matrices de interés ambiental por espectrofotometría en fase sólida (EFS)

A method for determining copper by solid phase spectrophotometry (SPS) was optimized using the Doehlert design. Copper(II) was sorbed on a styrene-divinylbenzene anion-exchange resin as a Cu(II)-1-(2-pyridylazo)-2-naphthol (PAN) complex, at pH 7.0. Resin phase absorbances at 560 and 800 nm were measured directly. The detection limit was found to be 2.5 µg L-1. The relative standard deviation on ten replicate determinations of 10 µg Cu(II) in 1000 mL samples was 1.1%. The linear range of the determination was 5.0-100 µg L-1. The method was applied successfully to the determination of Cu(II) in natural water and vegetable samples.

Heavy atom enhanced room-temperature phosphorimetry for ultratrace determination of harmane

Harmane has been proposed for the treatment of epilepsy, AIDS and leshmaniosis. Its room-temperature phosphorescence was induced using either AgNO3 or TlNO3, enabling absolute limits of detection of 0.12 and 2.4 ng respectively, with linear dynamic ranges extending up to 456 ng (AgNO3) and 911 ng (TlNO3). Relative standard deviations around 3% were observed for substrates containing 46 ng of harmane. Such sensitivity and precision are needed because harmane intake must be strictly controlled to achieve proper therapeutic response. Interference studies were performed using thalidomide, reserpine and yohimbine. Recovery of 104±6% was achieved using solid surface room-temperature phosphorimetry. The result was comparable to the one obtained by micellar electrokinetic chromatography.

Determination of aluminum in food samples after preconcentration as aluminon complex on microcrystalline naphthalene by spectrophotometry

A sensitive preconcentration procedure for spectrophotometeric determination of aluminum was developed. Aluminum as aluminon complex is adsorbed on microcrystalline naphthalene. The naphthalene containing the complex is dissolved in 3 mL of acetone and its absorbance is measured at 544 nm. The effect of various factors on the preconcentration of aluminum was investigated. The calibration graph was linear in the range of 1-60 mg L-1. The limit of detection was 0.52 mg L-1 and relative standard deviation for the determination of 5 mg L-1 was 2.65%. The proposed solid phase extraction procedure was applied to determination of aluminum in food samples.

Preconcentration, determination and speciation of iron by solid-phase extraction using dimethyl (E)-2-[(Z)-1-acetyl)-2-hydroxy-1-propenyl]-2-butenedioate

A new sensitive and selective procedure for speciation of trace dissolved Fe(III) and Fe(II), using modified octadecyl silica membrane disks and determination by flame atomic absorption spectrometry was developed. A ML3 complex is formed between the ligand and Fe(III) responsible for extraction of metal ion on the disk. Various factors influencing the separation of iron were investigated and the optimized operation conditions were established. Under optimum conditions, an enrichment factor of 166 was obtained for Fe3+ ions. The calibration graph using the preconcentration system for Fe3+ was linear between 40.0 and 1000.0 μg L-1.

Determinação de bifenilos policlorados em milho através de extração em fase sólida seguida de cromatografia a gás acoplada à espectrometria de massas

This paper describes an analytical method for analyzing polychlorinated biphenyls in corn samples using solid phase extraction (SPE) followed by determination by GC-MS. All calibration curves proved linear (r> 0.99). Recoveries ranged between 74.1 and 110.6% with relative standard deviation lower than 20% for all compounds. The limits of quantitation for the method were between 0.025 and 0.1 ng g-1. Of the 51 samples analyzed, PCB 180 showed the highest frequency, being detected in more than 39%, followed by PCB 138, detected in more than 33% of samples.