Photolithographic fabrication method of computer-generated holographic interferograms

We consider the fabrication of high-quality interferogram-type diffractive optical elements with conventional photolithographic techniques and compare the results with those achievable with electron-beam lithography. The fringes associated with the phase transfer function of the binary phase holographic interferogram are approximated with rectangles, which can be realized at submicron accuracy using a pattern generator and step-and-repeat camera. The effects of the rectangle quantization are analyzed both numerically and experimentally with the aid of diffraction patterns produced by simple focusing elements. Both resolution and diffraction efficiency of the best holograms approach their theoretical values

Ischemia-reperfusion syndrome in human renal transplantation : studies of the pathophysiological mechanisms

Renal transplantation represents the treatment of choice for the majority of patients with end-stage renal disease. Since the introduction of calcineurin inhibitor immunosuppressive drugs in the 1980s, we have witnessed a successful era for all solid organ transplantations. However, many kidneys continue to fail resulting from chronic allograft nephropathy years after transplantation. Increasing evidence from the last three decades suggests that early graft injury also jeopardizes long-term outcomes. As demand for renal transplants continues to rise, a better understanding of early allograft injury is required in order to develop protective interventions. This thesis focuses on the inflammatory mechanisms of early kidney graft injury as well as the differences in systemic inflammatory responses in patients following various immunosuppressive protocols. In total, 45 adult patients undergoing renal transplantation at Helsinki University Hospital were studied. Patients were recruited as a subset from a larger randomized study comparing three immunosuppressive protocols. Thus, 15 (group A), 14 (group B), and 16 (group C) patients were consecutively recruited retaining the original randomization. In group A, patients received perioperative a 9-mg/kg infusion of antithymocyte globulin complemented by a triple immunosuppression therapy consisting of reduced dose cyclosporine, azathioprine, and steroids. Group B patients received two doses of the interleukin 2 (IL-2) receptor antagonist basiliximab with a reduced dose cyclosporine triple therapy as in group A. Group C patients received a conventional triple immunosuppression therapy of 10-mg/kg cyclosporine, azathioprine, and steroids. Central vein blood samples were taken before surgery, before graft reperfusion, and during reperfusion. In addition, during reperfusion blood samples were also obtained directly from the renal graft artery and vein in order to study phenomena local to the graft vascular bed. From blood samples, various established biomarkers of inflammation and coagulation were determined complemented with measurements of the graft blood flow. The primary findings from this study consisted of the associations between the investigated inflammatory markers and the pathways with ensuing delayed graft function (DGF). Marked neutrophil sequestration in the renal graft was demonstrated immediately after reinstitution of the blood flow. Later, this was associated with a diminishing blood flow. Antithymocyte globulin (ATG) administration provided an unforeseen but unique opportunity to observe graft reflow under a systemic pro-inflammatory state. In this situation, avid graft uptake of APC was noted. Thus, this uptake may prove protective. Therefore, as a pharmaceutical preparation already exists, albeit for a different indication, new therapeutic interventions in the context of transplantation could be explored in the future.Valtaosalle loppuvaiheeseen edennyttä munuaistautia sairastavista potilaista paras hoitovaihtoehto on munuaisensiirto. Kuusikymmentäluvun kokeellisesta hoitomuodosta on kehittynyt nykypäivään tultaessa vakiintunutta toimintaa. Syklosporiini-lääke otettiin käyttöön neljä vuosikymmentä sitten, minkä jälkeen olemme saaneet todistaa elinsiirtojen voittokulkua. Edelleen kuitenkin vaikea ongelma on siirtomunuaiseen kehittyvä krooninen hyljintä, jonka vuoksi vuosien mittaan merkittävä määrä siirteistä menetetään. Noin kolmen vuosikymmenen tutkimusaineisto osoittaa, että siirteen varhaiset vauriot altistavat siirteen toiminnan heikkenemiselle ja siirteen menetykselle myös pitkällä aikavälillä. Koska siirtoa odottavia potilaita on jatkuvasti enemmän kuin tarjolla olevia siirteitä, parempi varhaisvaiheen vaurioiden ymmärtäminen olisi tärkeää suojaavien hoitojen ja toimenpiteiden kehittämiseksi. Tämä väitöskirjatutkimus keskittyy siirtomunuaista varhaisvaiheessa vaurioittavan tulehdusreaktion mekanismeihin, sekä eri hylkimisenestolääkityksiä käyttävien potilasryhmien tulehdusvasteiden eroihin. Tutkimukseemme osallistui neljäkymmentäviisi aikuista, joille tehtiin munuaisensiirto Helsingin yliopistollisessa keskussairaalassa. Potilaat rekrytoitiin osana tutkimusta, jossa vertailtiin kolmea erilaista hylkimisenestolääkitysohjelmaa. Potilasrekrytointi suoritettiin peräkkäin kustakin hylkimisenestolääkityksen ryhmästä säilyttäen alkuperäinen ryhmien satunnaistaminen. Ryhmässä A (15 potilasta) käytettiin leikkauksenaikaista 9mg/kg ATG infuusiota, alkuvaiheen matalaa syklosporiini-annostusta, atsatiopriinia ja kortikosteroideja. Ryhmässä B (14 potilasta) potilaat saivat kaksi infuusiota IL-2 -reseptorin estäjää basiliximabia ja muuten samanlaista, alkuvaiheessa matala-annoksista syklosporiinikolmoishoitoa kuten ryhmän A potilaatkin. Ryhmän C potilaat (16 potilasta) saivat traditionaalista kolmoishoitoa 10mg/kg syklosporiini-annostuksella, atsatiopriinilla ja kortikosteroideilla. Verinäytteet otettiin keskuslaskimosta ennen leikkausta, ennen siirteen reperfuusiota ja reperfuusion aikana. Tämän lisäksi reperfuusion aikana otettiin verinäytteet siirteen valtimosta ja laskimosta siirteen paikallisten ilmiöiden tarkastelemiseksi. Verinäytteistä määritettiin verenkuva sekä neutrofiilien ja monosyyttien CD11b ja L-selektiini –ekspressiot virtaussytometrialla. Edelleen plasmasta määritettiin laktoferriini-, tPA-, D-dimeeri-, protrombiinifragmentti 1 + 2 (F1+2), PAI-1, MMP9- ja TIMP-1 –pitoisuudet entsyymiimmunologisesti (ELISA). Proteiini-C ja aktivoitu proteiini-C määritettiin entsyymi-kaappaus – metodilla. Verenvirtaus siirteessä mitattiin pulssi-doppler virtausmittarilla. Tutkimuksen keskeisimmät tulokset koskevat tutkittujen markkerien assosiaatioita viivästyneeseen siirteen käynnistymiseen. Välittömästi verenkierron aukaisuun liittyen todettiin huomattava neutrofiilisolujen kertyminen siirteeseen. Tähän puolestaan liittyi viiveellä siirteen verenkierron heikentyminen. ATG-annostelu aiheutti ennaltaarvaamattoman proinflammatorisen reaktion, mikä tarjosi kiinnostavan mahdollisuuden tutkia munuaissiirteen verenkierron käynnistymistä systeemisen tulehdustilan vallitessa. Tutkimuksessamme totesimme ATG-ryhmässä siirteen kuluttavan runsaasti kiertävää aktivoitunutta proteiini-C:tä. On mahdollista, että aktivoituneen proteiini-C:n vaikutus voi tässä tilanteessa olla suojaava, mikä tarjoaa mahdollisuuden tulevaisuudessa lääkehoitotutkimuksiin

Raskaat harvinaiset maa-alkuaineet ja laakiobasalttien lähteet

Editor's ChoiceHeavy rare earth elements (HREEs) in mafic and ultramafic volcanic rocks are useful recorders of mantle source processes because their ratios are not easily modified by differentiation. Here we utilize REEBOX PRO, a simulator of adiabatic decompression melting of the mantle, to study the behavior of HREEs in the formation of continental flood basalt (CFB) parental magmas in the mantle. We simulate partial melting of depleted peridotite, pyrolitic peridotite, pyroxenite, and peridotite-pyroxenite mixtures at mantle potential temperatures of 1350-1650 degrees C and lithospheric thicknesses of 50-150 km, and compare the results to natural data. Many large igneous provinces are typified by low-Ti and high-Ti CFBs with contrasting HREE patterns. Our results show that low-Ti CFBs originate mainly from peridotitic sources. Flat mid-ocean ridge basalt-like HREE patterns typical of low-Ti CFBs can be generated beneath thick lithosphere (similar to 100 km), given that mantle potential temperatures are high (>1500 degrees C) and garnet is completely consumed from the source. We thus challenge the common interpretation that flat HREE patterns always indicate shallow sources for CFB parental magmas. High-Ti CFBs require pyroxenite-bearing sources (>= 10%). Contrary to a common view, their steep oceanic island basalt-like HREE patterns can be generated beneath quite a thin lithosphere (similar to 50 km), which is due to increased garnet stability in pyroxenite sources. When applied to CFBs of the Karoo large igneous province, the results are compatible with a model where a mantle plume penetrates a progressively thinning Gondwana lithosphere.Peer reviewe

Luenhan pikriitit keskisestä Mosambikista - Viestintuojia Karoon laakiobasalttien vaippapluumilähteestä?

We present geochemical and isotopic (Nd, Sr) data for a picrite lava suite from the Luenha River and adjacent areas in Mozambique. The Luenha picrites represent a previously unknown type of picrites related to the Karoo large igneous province (LIP) and are distinguished by their notably low TiO2 contents (0.3-1.0 wt%) and coupling of high Nb/Y with low Zr/Y and Sm/Yb. Relatively high CaO and low Zn/Fe point to a peridotitic mantle source. Contamination-sensitive incompatible element ratios show that one lava flow is likely to be uncontaminated by the crust and its composition suggests a mantle source with primitive mantle-like incompatible element ratios and mildly depleted isotopic ratios (initial Sr-87/Sr-86 = 0.7041 and epsilon(Nd) = +1.4 at 180 Ma). The primary melts of the Luenha picrites had MgO contents in the range of 13-21 wt%. Our preferred estimate for a primary melt composition (MgO = 18 wt%) resembles experimental melts of fertile mantle peridotite at 3-4 GPa and indicates liquidus temperature of 1445-1582 degrees C. Geochemical similarities suggest the Luenha picrites were generated from the same overall primitive mantle-like reservoir that produced the main volume of Karoo flood basalts in the Karoo, Kalahari, and Zambezi basins, whereas the previously identified enriched and depleted (upper) mantle sources of Karoo picrite suites (Mwenezi, Antarctica) were subordinate sources for flood basalts. We propose that the Luenha picrites record melting of a hot, chemically primitive mantle plume source that may have been rooted in the sub-African large low shear velocity province boundary and that such a source might have been the most significant magma source in the Karoo LIP. (C) 2019 The Author(s). Published by Elsevier B.V.Peer reviewe

Koulun mahdollisuudet lapsen oppimisen ja hyvinvoinnin vahvistajana – opettajat ja koulukuraattorit hyvinvointityön tarpeen tunnistajina ja koordinoijina.

Vertaisarvioit

Diffusion and Protein Corona Formation of Lipid-Based Nanoparticles in the Vitreous Humor : Profiling and Pharmacokinetic Considerations

The vitreous humor is the first barrier encountered by intravitreally injected nanoparticles. Lipid-based nanoparticles in the vitreous are studied by evaluating their diffusion with single-particle tracking technology and by characterizing their protein coronae with surface plasmon resonance and high-resolution proteomics. Single-particle tracking results indicate that the vitreal mobility of the formulations is dependent on their charge. Anionic and neutral formulations are mobile, whereas larger (>200 nm) neutral particles have restricted diffusion, and cationic particles are immobilized in the vitreous. PEGylation increases the mobility of cationic and larger neutral formulations but does not affect anionic and smaller neutral particles. Convection has a significant role in the pharmacokinetics of nanoparticles, whereas diffusion drives the transport of antibodies. Surface plasmon resonance studies determine that the vitreal corona of anionic formulations is sparse. Proteomics data reveals 76 differentially abundant proteins, whose enrichment is specific to either the hard or the soft corona. PEGylation does not affect protein enrichment. This suggests that protein-specific rather than formulation-specific factors are drivers of protein adsorption on nanoparticles in the vitreous. In summary, our findings contribute to understanding the pharmacokinetics of nanoparticles in the vitreous and help advance the development of nanoparticle-based treatments for eye diseases.Peer reviewe