Pre-eclampsia : The role of soluble VEGF receptor-1 and related anti-angiogenic factors beyond

Pre-eclampsia is a pregnancy complication that affects about 5% of all pregnancies. It is known to be associated with alterations in angiogenesis -related factors, such as vascular endothelial growth factor (VEGF). An excess of antiangiogenic substances, especially the soluble receptor-1 of VEGF (sVEGFR-1), has been observed in maternal circulation after the onset of the disease, probably reflecting their increased placental production. Smoking reduces circulating concentrations of sVEGFR-1 in non-pregnant women, and in pregnant women it reduces the risk of pre-eclampsia. Soluble VEGFR-1 acts as a natural antagonist of VEGF and placental growth factor (PlGF) in human circulation, holding a promise for potential therapeutic use. In fact, it has been used as a model to generate a fusion protein, VEGF Trap , which has been found effective in anti-angiogenic treatment of certain tumors and ocular diseases. In the present study, we evaluated the potential use of maternal serum sVEGFR-1, Angiopoietin-2 (Ang-2) and endostatin, three central anti-angiogenic markers, in early prediction of subsequent pre-eclampsia. We also studied whether smoking affects circulating sVEGFR-1 concentrations in pregnant women or their first trimester placental secretion and expression in vitro. Last, in order to allow future discussion on the potential therapy based on sVEGFR-1, we determined the biological half-life of endogenous sVEGFR-1 in human circulation, and measured the concomitant changes in free VEGF concentrations. Blood or placental samples were collected from a total of 268 pregnant women between the years 2001 2007 in Helsinki University Central Hospital for the purposes above. The biomarkers were measured using commercially available enzyme-linked immunosorbent assays (ELISA). For the analyses of sVEGFR-1, Ang-2 and endostatin, a total of 3 240 pregnant women in the Helsinki area were admitted to blood sample collection during two routine ultrasoundscreening visits at 13.7 ± 0.5 (mean ± SD) and 19.2 ± 0.6 weeks of gestation. Of them, 49 women later developing pre-eclampsia were included in the study. Their disease was further classified as mild in 29 and severe in 20 patients. Isolated early-onset intrauterine growth retardation (IUGR) was diagnosed in 16 women with otherwise normal medical histories and uncomplicated pregnancies. Fifty-nine women remaining normotensive, non-proteinuric and finally giving birth to normal-weight infants were picked to serve as the control population of the study. Maternal serum concentrations of Ang-2, endostatin and sVEGFR-1, were increased already at 16 20 weeks of pregnancy, about 13 weeks before the clinical manifestation of preeclampsia. In addition, these biomarkers could be used to identify women at risk with a moderate precision. However, larger patient series are needed to determine whether these markers could be applied for clinical use to predict preeclampsia. Intrauterine growth retardation (IUGR), especially if noted at early stages of pregnancy and not secondary to any other pregnancy complication, has been suggested to be a form of preeclampsia compromising only the placental sufficiency and the fetus, but not affecting the maternal endothelium. In fact, IUGR and preeclampsia have been proposed to share a common vascular etiology in which factors regulating early placental angiogenesis are likely to play a central role. Thus, these factors have been suggested to be involved in the pathogenesis of IUGR. However, circulating sVEGFR-1, Ang-2 and endostatin concentrations were unaffected by subsequent IUGR at early second trimester. Furthermore, smoking was not associated with alterations in maternal circulating sVEGFR-1 or its placental production. The elimination of endogenous sVEGFR-1 after pregnancy was calculated from serial samples of eight pregnant women undergoing elective Caesarean section. As typical for proteins in human compartments, the elimination of sVEGFR-1 was biphasic, containing a rapid halflife of 3.4 h and a slow one of 29 h. The decline in sVEGFR-1 concentrations after mid-trimester legal termination of pregnancy was accompanied with a simultaneous increase in the serum levels of free VEGF so that within a few days after pregnancy VEGF dominated in the maternal circulation. Our study provides novel information on the kinetics of endogenous sVEGFR-1, which serves as a potential tool in the development of new strategies against diseases associated with angiogenic imbalance and alterations in VEGF signaling.

The contribution of polarons, bipolarons and intersite tunneling to low temperature conductivity in doped polypyrrole

The conductivity of highly doped polypyrrole is less than that of intermediately doped samples, by two orders of magnitude, at 4.2 K. This may be due to more number of bipolarons in highly doped samples. Bipolarons require four times more activation energy than single polarons to hop by thermally induced virtual transitions to intermediate dissociated polaron states than by the nondissociated process. The conduction process in these polyconjugated systems involve ionization from deep trapped states, having a View the MathML source dependence, hopping from localised states, having View the MathML source dependence, and intersite tunnel percolation, having T−1 dependence. The interplay of these factors leads to a better fit by View the MathML source. The mechanism for this exponential behaviour need not be same as that of Motts variable range hopping. Conduction by percolation is possible, if an infinite cluster of chains can be connected by impurity centers created by dopant ions. The tendency for the saturation of conductivity at very low temperatures is due to the possibility of intersite tunnel percolation is disordered polaronic systems.

Ruismallasuute vähägluteenisessa kauraleivonnassa

Tutkielman kirjallisuuskatsauksessa tarkasteltiin kauran leivontateknologisia ominaisuuksia, entsyymiaktiivista leivontaa ja ruismaltaan hyödyntämistä vähägluteenisessa leivonnassa. Kokeellisessa osiossa tutkittiin ruismallashapantaikinasta valmistetun uutteen vaikutusta kaurataikinan viskositeettiin ja kauraleivän ominaisuuksiin. Työn tarkoituksena oli kehittää maultaan ja rakenteeltaan onnistunut rukiinmakuinen kauraleipä. Ruismaltaan entsyymien annettiin pilkkoa keliaakikolle haitallisia rukiin prolamiineja hapantaikinaprosessissa. Hapantaikinasta erotettiin uute sentrifugoimalla. Leivontakokeisiin käytettiin entsyymiaktiivista ja kuumentamalla inaktivoitua uutetta. Uutteella korvattiin taikinavettä 15, 25 ja 30 % (taikinan painosta). Leivonta toteutettiin miniatyyrikoossa, vuokaleivontana 20 g:n taikinapaloja käyttäen. Taikinoiden viskositeetti mitattiin tarkoituksena seurata beetaglukaanin hydrolyysiä. Rukiin makua mitattiin koulutetun raadin avulla. Happaman uutteen lisäys laski taikinan pH-arvoa noin 5,8:sta noin 4,4:ään. Entsyymiaktiivisen uutteen lisäys laski taikinan viskositeettia ja inaktivoitu uute puolestaan kasvatti sitä. Leipien sisus tiivistyi, jolloin mitatut sisuksen kovuudet kasvoivat uutteen lisäyksen myötä. Uutelisäys paransi leipien makua ja aromia. Uutteen vaikutuksesta leipien huokoset olivat pienempiä ja ne jakaantuivat tasaisemmin leipämatriisiin. Jos uutetta käytettiin inaktivoituna, leipien murenevuus kasvoi. Tutkimuksessa kehitetyn teknologian avulla oli mahdollista valmistaa hyvänlaatuinen, rukiinmakuinen kauraleipä myös ilman että uutteen entsyymit inaktivoitiin keittämällä. Tähän vaikutti ilmeisesti taikinan alhainen pH, joka inhiboi alfa-amylaasia, ja kauratärkkelyksen korkea liisteröitymislämpötila, jolloin entsyymien inaktivoituminen paiston aikana tapahtui ennen kuin tärkkelys tuli alttiiksi liialliselle pilkkoutumiselle. Tämä mahdollistaa uutteen käytön osana leivontaprosessia ilman inaktivointia. Hapantaikinafermentaatio osana gluteenitonta leivontaa havaittiin toimivaksi yhdistelmäksi, sillä se paransi leivän väriä, makua ja rakennetta. Myös leivän homeeton aika parani jo vähäisenkin uutelisäyksen vaikutuksesta. Näyttää siltä, että tämän teknologian avulla on mahdollista tuoda esille pitkään kaivattua rukiin makua vähägluteenisten kauraleipien valikoimassa. Laskennallisesti ja aiempiin tuloksiin tukeutuen, voitiin päätellä, että leivän prolamiinipitoisuudessa on mahdollista päästä tasolle 63,5 mg/kg, mutta jatkokehityksen avulla päästäisiin luultavasti vielä parempiin tuloksiin.

An infrared spectroscopic study of the low-spin-high-spin transition in FexMn1-x(Phen)2(NCS)2: A composition-induced change in the order of the spin-state transition

Infrared spectroscopy provides a valuable tool to investigate the spin-state transition in Fe(II) complexes of the type Fe(Phen)2(NCS)2. With progressive substitution of Fe by Mn, the first-order transition changes over to a second-order transition, with a high residual population of the high-spin state even at very low temperatures

Microsomal redox systems in brown adipose tissue: high lipid peroxidation, low cholesterol biosynthesis and no detectable cytochrome P-450

The presence of redox systems in microsomes of brown adipose tissue (BAT) in cold exposed rats was investigated and compared with liver. BAT microsomes showed high activity of lipid peroxidation measured both by the formation of malondialdehyde (MDA) and by oxygen uptake. NADH and NADPH dependent cytochrome c reductase activity were present in both BAT and liver microsomes. Aminopyrine demethylase and aniline hydroxylase activities, the characteristic detoxification enzymes in liver microsomes could not be detected in BAT microsomes. BAT minces showed very poor incorporation of [1-14C]acetate and [2-14C]-mevalonate in unsaponifiable lipid fraction compared to liver. Biosynthesis of cholesterol and ubiquinone, but not fatty acids, and the activity of 3-hydroxy-3-methyl glutaryl CoA reductase appear to be very low in BAT. Examination of difference spectra showed the presence of only cytochrome b 5 in BAT microsomes. In addition to the inability to detect the enzyme activities dependent on cytochrome P-450, a protein with the characteristic spectrum, molecular size in SDS-PAGE and interaction with antibodies in double diffusion test, also could not be detected in BAT microsomes. The high activity of lipid peroxidation in microsomes, being associated with large oxygen uptake and oxidation of NADPH, will also contribute to the energy dissipation as heat in BAT, considered important in thermogenesis.

Theoretical and Computational Analysis of Static and Dynamic Anomalies in Water-DMSO Binary Mixture at Low DMSO Concentrations

Experiments have repeatedly observed both thermodynamic and dynamic anomalies in aqueous binary mixtures, surprisingly at low solute concentration. Examples of such binary mixtures include water-DMSO, water-ethanol, water-tertiary butyl alcohol (TBA), and water-dioxane, to name a few. The anomalies have often been attributed to the onset of a structural transition, whose nature, however, has been left rather unclear. Here we study the origin of such anomalies using large scale computer simulations and theoretical analysis in water-DMSO binary mixture. At very low DMSO concentration (below 10%), small aggregates of DMSO are solvated by water through the formation of DMSO-(H2O)(2) moieties. As the concentration is increased beyond 10-12% of DMSO, spanning clusters comprising the same moieties appear in the system. Those clusters are formed and stabilized not only through H-bonding but also through the association of CH3 groups of DMSO. We attribute the experimentally observed anomalies to a continuum percolation-like transition at DMSO concentration X-DMSO approximate to 12-15%. The largest cluster size of CH3-CH3 aggregation clearly indicates the formation of such percolating clusters. As a result, a significant slowing down is observed in the decay of associated rotational auto time correlation functions (of the S = O bond vector of DMSO and O-H bond vector of water). Markedly unusual behavior in the mean square fluctuation of total dipole moment again suggests a structural transition around the same concentration range. Furthermore, we map our findings to an interacting lattice model which substantiates the continuum percolation model as the reason for low concentration anomalies in binary mixtures where the solutes involved have both hydrophilic and hydrophobic moieties.

Characterization of lysozyme crystals with unusually low solvent content

Studies on the low-humidity (88%) forms of tetragonal and monoclinic lysozyme, resulting from water-mediated transformations, have provided a wealth of information on the variability in protein hydration, its structural consequences and the water structure associated with proteins, in addition to facilitating the delineation of the rigid and the flexible regions in the protein molecule and the invariant features in its hydration shell. Surprisingly, monoclinic lysozyme continues to diffract even when the environmental humidity is drastically reduced, thus permitting the structural study of the enzyme at different levels of hydration. As part of a study in this direction, three very low humidity forms, two of them occuring at a nominal relative humidity of 38% and the other at 5% relative humidity, have been characterized. These have unprecedented low solvent contents of 16.9, 17.6 and 9.4%, respectively, as determined by the Matthews method.

Discontinuous shear thickening in confined dilute carbon nanotube suspensions

A monotonic decrease in viscosity with increasing shear stress is a known rheological response to shear flow in complex fluids in general and for flocculated suspensions in particular. Here we demonstrate a discontinuous shear-thickening transition on varying shear stress where the viscosity jumps sharply by four to six orders of magnitude in flocculated suspensions of multiwalled carbon nanotubes (MWNT) at very low weight fractions (approximately 0.5%). Rheooptical observations reveal the shear-thickened state as a percolated structure of MWNT flocs spanning the system size. We present a dynamic phase diagram of the non-Brownian MWNT dispersions revealing a starting jammed state followed by shear-thinning and shear-thickened states. The present study further suggests that the shear-thickened state obtained as a function of shear stress is likely to be a generic feature of fractal clusters under flow, albeit under confinement. An understanding of the shear-thickening phenomena in confined geometries is pertinent for flow-controlled fabrication techniques in enhancing the mechanical strength and transport properties of thin films and wires of nanostructured composites as well as in lubrication issues.

Studies on age-hardening characteristics of ceramic particle/matrix interfaces in Al-Cu-SiCp composites using ultra low-load-dynamic microhardness measurements

Ultra low-load-dynamic microhardness testing facilitates the hardness measurements in a very low volume of the material and thus is suited for characterization of the interfaces in MMC's. This paper details the studies on age-hardening behavior of the interfaces in Al-Cu-5SiC(p) composites characterized using this technique. Results of hardness studies have been further substantiated by TEM observations. In the solution-treated condition, hardness is maximum at the particle/matrix interface and decreases with increasing distance from the interface. This could be attributed to the presence of maximum dislocation density at the interface which decreases with increasing distance from the interface. In the case of composites subjected to high temperature aging, hardening at the interface is found to be faster than the bulk matrix and the aging kinetics becomes progressively slower with increasing distance from the interface. This is attributed to the dislocation density gradient at the interface, leading to enhanced nucleation and growth of precipitates at the interface compared to the bulk matrix. TEM observations reveal that the sizes of the precipitates decrease with increasing distance from the interface and thus confirms the retardation in aging kinetics with increasing distance from the interface.

X-Codes: A Low Complexity Full-Rate High-Diversity Achieving Precoder for TDD MIMO Systems

We consider a time division duplex multiple-input multiple-output (nt × nr MIMO). Using channel state information (CSI) at the transmitter, singular value decomposition (SVD) of the channel matrix is performed. This transforms the MIMO channel into parallel subchannels, but has a low overall diversity order. Hence, we propose X-Codes which achieve a higher diversity order by pairing the subchannels, prior to SVD preceding. In particular, each pair of information symbols is encoded by a fixed 2 × 2 real rotation matrix. X-Codes can be decoded using nr very low complexity two-dimensional real sphere decoders. Error probability analysis for X-Codes enables us to choose the optimal pairing and the optimal rotation angle for each pair. Finally, we show that our new scheme outperforms other low complexity precoding schemes.

Starting scheme for load commutated inverter-fed wound field synchronous machine using an auxiliary low-power voltage source inverter

Conventional thyristor-based load commutated inverter (LCI)-fed wound field synchronous machine operates only above a minimum speed that is necessary to develop enough back emf to ensure commutation. The drive is started and brought up to a speed of around 10-15% by a complex `dc link current pulsing' technique. During this process, the drive have problems such as pulsating torque, insufficient average starting torque, longer starting time, etc. In this regard a simple starting and low-speed operation scheme, by employing an auxiliary low-power voltage source inverter (VSI) between the LCI and the machine terminals, is presented in this study. The drive is started and brought up to a low speed of around 15% using the VSI alone with field oriented control. The complete control is then smoothly and dynamically transferred to the conventional LCI control. After the control transfer, the VSI is turned off and physically disconnected from the main circuit. The advantages of this scheme are smooth starting, complete control of torque and flux at starting and low speeds, less starting time, stable operation, etc. The voltage rating of the required VSI is very low of the order of 10-15%, whereas the current rating is dependent on the starting torque requirement of the load. The experimental results from a 15.8 hp LCI-fed wound field synchronous machine are given to demonstrate the scheme.

Numerical Study Of Heat Transfer From Pin Fin Heat Sink Using Steady And Pulsated Impinging Jets

The work reported in this thesis is an attempt to enhance heat transfer in electronic devices with the use of impinging air jets on pin-finned heat sinks. The cooling per-formance of electronic devices has attracted increased attention owing to the demand of compact size, higher power densities and demands on system performance and re-liability. Although the technology of cooling has greatly advanced, the main cause of malfunction of the electronic devices remains overheating. The problem arises due to restriction of space and also due to high heat dissipation rates, which have increased from a fraction of a W/cm2to 100s of W /cm2. Although several researchers have at-tempted to address this at the design stage, unfortunately the speed of invention of cooling mechanism has not kept pace with the ever-increasing requirement of heat re- moval from electronic chips. As a result, efficient cooling of electronic chip remains a challenge in thermal engineering. Heat transfer can be enhanced by several ways like air cooling, liquid cooling, phase change cooling etc. However, in certain applications due to limitations on cost and weight, eg. air borne application, air cooling is imperative. The heat transfer can be increased by two ways. First, increasing the heat transfer coefficient (forced convec- tion), and second, increasing the surface area of heat transfer (finned heat sinks). From previous literature it was established that for a given volumetric air flow rate, jet im-pingement is the best option for enhancing heat transfer coefficient and for a given volume of heat sink material pin-finned heat sinks are the best option because of their high surface area to volume ratio. There are certain applications where very high jet velocities cannot be used because of limitations of noise and presence of delicate components. This process can further be improved by pulsating the jet. A steady jet often stabilizes the boundary layer on the surface to be cooled. Enhancement in the convective heat transfer can be achieved if the boundary layer is broken. Disruptions in the boundary layer can be caused by pulsating the impinging jet, i.e., making the jet unsteady. Besides, the pulsations lead to chaotic mixing, i.e., the fluid particles no more follow well defined streamlines but move unpredictably through the stagnation region. Thus the flow mimics turbulence at low Reynolds number. The pulsation should be done in such a way that the boundary layer can be disturbed periodically and yet adequate coolant is made available. So, that there is not much variation in temperature during one pulse cycle. From previous literature it was found that square waveform is most effective in enhancing heat transfer. In the present study the combined effect of pin-finned heat sink and impinging slot jet, both steady and unsteady, has been investigated for both laminar and turbulent flows. The effect of fin height and height of impingement has been studied. The jets have been pulsated in square waveform to study the effect of frequency and duty cycle. This thesis attempts to increase our understanding of the slot jet impingement on pin-finned heat sinks through numerical investigations. A systematic study is carried out using the finite-volume code FLUENT (Version 6.2) to solve the thermal and flow fields. The standard k-ε model for turbulence equations and two layer zonal model in wall function are used in the problem Pressure-velocity coupling is handled using the SIMPLE algorithm with a staggered grid. The parameters that affect the heat transfer coefficient are: height of the fins, total height of impingement, jet exit Reynolds number, frequency of the jet and duty cycle (percentage time the jet is flowing during one complete cycle of the pulse). From the studies carried out it was found that: a) beyond a certain height of the fin the rate of enhancement of heat transfer becomes very low with further increase in height, b) the heat transfer enhancement is much more sensitive to any changes at low Reynolds number than compared to high Reynolds number, c) for a given total height of impingement the use of fins and pulsated jet, increases the effective heat transfer coefficient by almost 200% for the same average Reynolds number, d) for all the cases it was observed that the optimum frequency of impingement is around 50 − 100 Hz and optimum duty cycle around 25-33.33%, e) in the case of turbulent jets the enhancement in heat transfer due to pulsations is very less compared to the enhancement in case of laminar jets.

Antihyperlipidemic potential of Cedrus deodara extracts in monosodium glutamate induced obesity in neonatal rats

Objective: To study the antihyperlipidemic effect of Cedrus deodara (C. deodara) against monosodium glutamate (MSG) induced obesity in neonatal rats. Materials and Methods: The studies were carried out on newborn neonatal rats and were injected intraperitoneally with 2 mg/g of MSG on the 2(nd) and 4(th) postnatal days and 4 mg/g on 6(th), 8(th) and 10(th) postnatal days. Ethanolic extract (EE) and acetone extract (AE) of C. deodara was administered in a dose of 100 and 200 mg/kg, p.o./day at the age of 65 days. On day 60 of treatment, body weight, locomotor activity, body temperature, and various biochemical parameters like serum glucose, total cholesterol, triglyceride, and organs weights were recorded. Results: There was a significant reduction in body weight, organs and increased body temperature, locomotor activity after treatment with extracts. C. deodara decreased serum glucose, total cholesterol and triglyceride, low density lipoprotein (LDL) and very low density lipoprotein (VLDL) levels and increased high density lipoprotein (HDL) significantly has compared to MSG-control rats. Conclusion: C. deodara extracts exhibited antihyperlipidemic effect and it possesses anti-obesity properties in MSG induced obese rats.

Pulsed plasma treatment of polluted gas using wet/low temperature corona reactors

pplication of pulsed plasma for gas cleaning is gaining prominence in recent years mainly from the energy consideration point of view. Normally, gas treatment is carried out, at or above room temperature, by a conventional dry type corona reactor. However, this treatment is still inadequate in the removal of certain stable gases present in the exhaust/flue gas mixture. The authors report some interesting results of the treatment of such stable gases with pulsed plasma at very low ambient temperature. Also reported in the paper is an improvement in DeNO/DeNOx efficiency using unconventional wet-type reactors, designed and fabricated by the authors, operating at different ambient temperatures. Apart from laboratory tests on simulated gas mixtures, field tests were also carried out on the exhaust gas of a 8 kW diesel engine. Further, an attempt was made to test the feasibility of a helical wire as a corona electrode in place of the conventional straight wire electrode. A comparative analysis of the various tests is presented together with a note on the energy consideration

Pulsed plasma treatment of polluted gas using wet/low temperature corona reactors

Application of pulsed plasma for gas cleaning is gaining prominence in recent years mainly from the energy consideration point of view. Normally, gas treatment is carried out, at or above room temperature, by a conventional dry type corona reactor. However, this treatment is still inadequate in the removal of certain stable gases present in the exhaust/flue gas mixture. The authors report some interesting results of the treatment of such stable gases with pulsed plasma at very low ambient temperature. Also reported in the paper is an improvement in DeNO/DeNOx efficiency using unconventional wet-type reactors, designed and fabricated by the authors, operating at different ambient temperatures. Apart from laboratory tests on simulated gas mixtures, field tests were also carried out on the exhaust gas of a 8 kW diesel engine. Further, an attempt was made to test the feasibility of a helical wire as a corona electrode in place of the conventional straight wire electrode. A comparative analysis of the various tests is presented together with a note on the energy consideration