111,893 research outputs found
European policies for social inclusion of Roma : Catch 22?
Get PDFThe article analyzes contemporary political discourses with regard to social inclusion of Roma on the basis of comparison with achievements and failures in the previous historical period of the communist rule in Eastern Europe. It argues that since the vast majority of the European Roma had lived in the past and continue living nowadays in the countries of Eastern Europe, no successful policy for their inclusion is possible without taking into account the experiences and outcomes of the actions for Roma integration in the socialist period. The experience from the times of socialism shows that successful policies are possible only in an appropriate socio-political context and only if accomplished within the mainstream approach. Against this background, the article scrutinizes the European Policies for Social Inclusion of Roma, and explains why they present a Catch 22 situation: There is a vicious cycle of problems which need to be solved; the solution requires a special policy for inclusion, however this policy stigmatizes Roma and sets them even more apart from the rest of society. Thus the vicious cycle of problems expands. The main point of the article is to propose an explanation of this failure of democracy and liberalism, which could constitute a useful lesson for the future.Peer reviewe
Punasolut ja uudet nanomateriaalit: kohti nanoturvallisuutta ja nanolääketiedettä
No full textAbstractNanomaterials are an essential part of modern life due to their extensive use in industrial and commercial products and future personalized medicine. In recent years, new nanoparticles (NPs) have been introduced in bioimaging, diagnostics, drug delivery, and therapy. Along with the production growth of NPs, concerns about NPs safety for human health have been raised. As blood is an inevitable target for NP-based pharmaceutics at systemic NP-based drug administration, the investigation of the poorly understood effects of NPs on blood properties is of high demand.The present thesis focuses on the assessment of commercial and novel synthesized NPs towards the haemorheologica l properties of the main blood cellular component — red blood cells (RBCs). In the research for this thesis, RBC morphology, deformability and mutual interactions were examined at non-haemolytic concentrations of NPs. A revolutionary optical tweezers technique revealed subtle effects of indirect toxicity towards mutual RBCs interactions and deformability. Further, additional conventional optical microscopy analysis revealed the influence of NPs on RBC interactions on a multicellular level, while scanning electron microscopy (SEM) enabled high-resolution monitoring of RBCs surfaces and morphological alterations triggered by NPs. Another aim of the study addressed the unclear mechanism behind RBC interactions. Experimental evidence of the definitive role of the size and proportion of macromolecules in RBC interactions was provided. The mixture of natural polymer dextran mimicking plasma protein composition induced an RBC interaction mode similar to one observed in blood plasma. Thus, the new hybrid model combining “cross-bridges” and “depletion” effects was proposed.The reported findings contribute to the fundamental understanding of RBC interactions and can help to facilitate the design and clinical validation of polymer-based plasma expanders and novel NPs for safe and beneficial use.Original papersOriginal papers are not included in the electronic version of the dissertation.Avsievich, T., Zhu, R., Popov, A., Bykov, A., & Meglinski, I. (2022). Blood–nanomaterials interactions. In A. Denizli. T. Nguyen, R. Mariappan, M. Feroz Alam, & K. Khaliqur Rahman (Eds.), Nanotechnology for Hematology, Blood Transfusion, and Artificial Blood (pp. 1–40). Elsevier. https://doi.org/10.1016/B978-0-12-823971-1.00002-7Avsievich, T., Zhu, R., Popov, A., Bykov, A., & Meglinski, I. (2020). The advancement of blood cell research by optical tweezers. Reviews in Physics, 5, 100043. https://doi.org/10.1016/j.revip.2020.100043Self-archived versionAvsievich, T., Popov, A., Bykov, A., & Meglinski, I. (2018). Mutual interaction of red blood cells assessed by optical tweezers and scanning electron microscopy imaging. Optics Letters, 43(16), 3921–3924. https://doi.org/10.1364/OL.43.003921Self-archived versionAvsievich, T., Tarakanchikova, Y., Zhu, R., Popov, A., Bykov, A., Skovorodkin, I., Vainio, S., & Meglinski, I. (2019). Impact of nanocapsules on red blood cells interplay jointly assessed by optical tweezers and microscopy. Micromachines, 11(1), 19. https://doi.org/10.3390/mi11010019Self-archived versionAvsievich, T., Tarakanchikova, Y. V., Popov, A., Karmenyan, A., Bykov, A., & Meglinski, I. (2019). Combined use of optical tweezers and scanning electron microscopy to reveal influence of nanoparticles on red blood cells interactions. In A. Amelink, & S. K. Nadkarni (Eds.), Novel Biophotonics Techniques and Applications V (110750F). Proceedings of SPIE, 11075. https://doi.org/10.1117/12.2526730Self-archived versionAvsievich, T., Popov, A., Bykov, A., & Meglinski, I. (2019). Mutual interaction of red blood cells influenced by nanoparticles. Scientific Reports, 9(1), 5147. https://doi.org/10.1038/s41598-019-41643-xSelf-archived versionAvsievich, T., Zhu, R., Popov, A., Yatskovskiy, A., Popov, A. A., Tikhonowsky, G., Pastukhov, A., Klimentov, S., Bykov, A., Kabashin, A., & Meglinski, I. (2022). Hemorheological alterations of erythrocytes induced by plasmonic nanoparticles. Manuscript submitted for publication.TiivistelmäNanomateriaalit ovat olennainen osa nykyaikaista elämäntapaa, sillä niitä käytetään laajasti teollisissa ja kaupallisissa tuotteissa sekä tulevaisuuden yksilöllisessä lääketieteessä. Viime vuosina uusia nanopartikkeleita (NP) on otettu käyttöön biolääketieteellisessä kuvantamisessa ja diagnostiikassa sekä lääkkeiden antamisessa ja terapiassa. NP:iden tuotannon kasvun myötä on noussut esiin huoli niiden turvallisuudesta ihmisten terveydelle. Koska veri on väistämätön kohde NP-pohjaisille lääkkeille systeemisessä NP-pohjaisessa lääkkeen annossa, on nanopartikkelien vähän tutkittujen, veren ominaisuuksiin kohdistuvien vaikutusten selvittämiselle suuri tarve.Kyseinen opinnäytetyö keskittyy kaupallisten ja uusien syntetisoitujen nanaopartikkelien arviointiin verisolujen pääkomponentin eli punasolujen (RBC) hemorheologisten ominaisuuksien osalta. Tämän työn tutkimuksessa tarkasteltiin punasolujen morfologiaa, muodonmuutoksia ja keskinäisiä vuorovaikutuksia ei-hemolyyttisissä NP-pitoisuuksissa. Vallankumouksellinen optinen pinsettitekniikka paljasti epäsuoran myrkyllisyyden hienovaraiset vaikutukset punasolujen keskinäiseen vuorovaikutukseen ja muodonmuutokseen. Lisäksi tavanomainen optinen mikroskopia-analyysi paljasti NP:iden ja RBC:n vuorovaikutukset monisoluisella tasolla, kun taas pyyhkäisyelektronimikroskopia (SEM) mahdollisti punasolujen pintojen ja NP:iden laukaisemien morfologisten muutosten korkearesoluutioisen seurannan. Tutkimuksen toisena tavoitteena oli selvittää punasolujen vuorovaikutuksen taustalla olevaa epäselvää mekanismia. Työssä esitettiin kokeellisia todisteita makromolekyylien koon ja osuuden lopullisesta roolista punasolujen vuorovaikutuksessa. Plasmaproteiinikoostumusta jäljittelevän luonnollisen polymeerin dekstraanin seos indusoi punasolujen vuorovaikutusmuodon, joka on samanlainen kuin veriplasmassa havaittu. Siten työssä ehdotettiin uutta "ristisiltoja" ja "tyhjennystä” yhdistävää hybridimallia.Raportoidut löydökset auttavat ymmärtämään punasolujen vuorovaikutuksia ja voivat helpottaa polymeeripohjaisten plasmalaajenninten ja uusien nanopartikkelien suunnittelua sekä niiden kliinistä validointia turvallisen ja hyödyllisen käytön mahdollistamiseksi.OsajulkaisutOsajulkaisut eivät sisälly väitöskirjan elektroniseen versioon.Avsievich, T., Zhu, R., Popov, A., Bykov, A., & Meglinski, I. (2022). Blood–nanomaterials interactions. In A. Denizli. T. Nguyen, R. Mariappan, M. Feroz Alam, & K. Khaliqur Rahman (Eds.), Nanotechnology for Hematology, Blood Transfusion, and Artificial Blood (pp. 1–40). Elsevier. https://doi.org/10.1016/B978-0-12-823971-1.00002-7Avsievich, T., Zhu, R., Popov, A., Bykov, A., & Meglinski, I. (2020). The advancement of blood cell research by optical tweezers. Reviews in Physics, 5, 100043. https://doi.org/10.1016/j.revip.2020.100043Rinnakkaistallennettu versioAvsievich, T., Popov, A., Bykov, A., & Meglinski, I. (2018). Mutual interaction of red blood cells assessed by optical tweezers and scanning electron microscopy imaging. Optics Letters, 43(16), 3921–3924. https://doi.org/10.1364/OL.43.003921Rinnakkaistallennettu versioAvsievich, T., Tarakanchikova, Y., Zhu, R., Popov, A., Bykov, A., Skovorodkin, I., Vainio, S., & Meglinski, I. (2019). Impact of nanocapsules on red blood cells interplay jointly assessed by optical tweezers and microscopy. Micromachines, 11(1), 19. https://doi.org/10.3390/mi11010019Rinnakkaistallennettu versioAvsievich, T., Tarakanchikova, Y. V., Popov, A., Karmenyan, A., Bykov, A., & Meglinski, I. (2019). Combined use of optical tweezers and scanning electron microscopy to reveal influence of nanoparticles on red blood cells interactions. In A. Amelink, & S. K. Nadkarni (Eds.), Novel Biophotonics Techniques and Applications V (110750F). Proceedings of SPIE, 11075. https://doi.org/10.1117/12.2526730Rinnakkaistallennettu versioAvsievich, T., Popov, A., Bykov, A., & Meglinski, I. (2019). Mutual interaction of red blood cells influenced by nanoparticles. Scientific Reports, 9(1), 5147. https://doi.org/10.1038/s41598-019-41643-xRinnakkaistallennettu versioAvsievich, T., Zhu, R., Popov, A., Yatskovskiy, A., Popov, A. A., Tikhonowsky, G., Pastukhov, A., Klimentov, S., Bykov, A., Kabashin, A., & Meglinski, I. (2022). Hemorheological alterations of erythrocytes induced by plasmonic nanoparticles. Manuscript submitted for publication.Academic dissertation to be presented with the assent of the Doctoral Programme Committee of Information Technology and Electrical Engineering of the University of Oulu for public defence in the OP auditorium (L10), Linnanmaa, on 10 October 2022, at 12 noonAbstract
Nanomaterials are an essential part of modern life due to their extensive use in industrial and commercial products and future personalized medicine. In recent years, new nanoparticles (NPs) have been introduced in bioimaging, diagnostics, drug delivery, and therapy. Along with the production growth of NPs, concerns about NPs safety for human health have been raised. As blood is an inevitable target for NP-based pharmaceutics at systemic NP-based drug administration, the investigation of the poorly understood effects of NPs on blood properties is of high demand.
The present thesis focuses on the assessment of commercial and novel synthesized NPs towards the haemorheologica l properties of the main blood cellular component — red blood cells (RBCs). In the research for this thesis, RBC morphology, deformability and mutual interactions were examined at non-haemolytic concentrations of NPs. A revolutionary optical tweezers technique revealed subtle effects of indirect toxicity towards mutual RBCs interactions and deformability. Further, additional conventional optical microscopy analysis revealed the influence of NPs on RBC interactions on a multicellular level, while scanning electron microscopy (SEM) enabled high-resolution monitoring of RBCs surfaces and morphological alterations triggered by NPs. Another aim of the study addressed the unclear mechanism behind RBC interactions. Experimental evidence of the definitive role of the size and proportion of macromolecules in RBC interactions was provided. The mixture of natural polymer dextran mimicking plasma protein composition induced an RBC interaction mode similar to one observed in blood plasma. Thus, the new hybrid model combining “cross-bridges” and “depletion” effects was proposed.
The reported findings contribute to the fundamental understanding of RBC interactions and can help to facilitate the design and clinical validation of polymer-based plasma expanders and novel NPs for safe and beneficial use.Tiivistelmä
Nanomateriaalit ovat olennainen osa nykyaikaista elämäntapaa, sillä niitä käytetään laajasti teollisissa ja kaupallisissa tuotteissa sekä tulevaisuuden yksilöllisessä lääketieteessä. Viime vuosina uusia nanopartikkeleita (NP) on otettu käyttöön biolääketieteellisessä kuvantamisessa ja diagnostiikassa sekä lääkkeiden antamisessa ja terapiassa. NP:iden tuotannon kasvun myötä on noussut esiin huoli niiden turvallisuudesta ihmisten terveydelle. Koska veri on väistämätön kohde NP-pohjaisille lääkkeille systeemisessä NP-pohjaisessa lääkkeen annossa, on nanopartikkelien vähän tutkittujen, veren ominaisuuksiin kohdistuvien vaikutusten selvittämiselle suuri tarve.
Kyseinen opinnäytetyö keskittyy kaupallisten ja uusien syntetisoitujen nanaopartikkelien arviointiin verisolujen pääkomponentin eli punasolujen (RBC) hemorheologisten ominaisuuksien osalta. Tämän työn tutkimuksessa tarkasteltiin punasolujen morfologiaa, muodonmuutoksia ja keskinäisiä vuorovaikutuksia ei-hemolyyttisissä NP-pitoisuuksissa. Vallankumouksellinen optinen pinsettitekniikka paljasti epäsuoran myrkyllisyyden hienovaraiset vaikutukset punasolujen keskinäiseen vuorovaikutukseen ja muodonmuutokseen. Lisäksi tavanomainen optinen mikroskopia-analyysi paljasti NP:iden ja RBC:n vuorovaikutukset monisoluisella tasolla, kun taas pyyhkäisyelektronimikroskopia (SEM) mahdollisti punasolujen pintojen ja NP:iden laukaisemien morfologisten muutosten korkearesoluutioisen seurannan. Tutkimuksen toisena tavoitteena oli selvittää punasolujen vuorovaikutuksen taustalla olevaa epäselvää mekanismia. Työssä esitettiin kokeellisia todisteita makromolekyylien koon ja osuuden lopullisesta roolista punasolujen vuorovaikutuksessa. Plasmaproteiinikoostumusta jäljittelevän luonnollisen polymeerin dekstraanin seos indusoi punasolujen vuorovaikutusmuodon, joka on samanlainen kuin veriplasmassa havaittu. Siten työssä ehdotettiin uutta "ristisiltoja" ja "tyhjennystä” yhdistävää hybridimallia.
Raportoidut löydökset auttavat ymmärtämään punasolujen vuorovaikutuksia ja voivat helpottaa polymeeripohjaisten plasmalaajenninten ja uusien nanopartikkelien suunnittelua sekä niiden kliinistä validointia turvallisen ja hyödyllisen käytön mahdollistamiseksi
Lasersäteilyn indusoimien veren punasolujen ja hemoreologisten muutosten vuorovaikutusten erikoispiirteet
No full textAbstractThis thesis reports on studies of the fundamental interaction dynamics of human red blood cells (RBC) by optical tweezers (OT) and the application of the OT-based RBC-investigation protocol in facilitating blood photobiomodulation research at a single-cell level. The motivation for the present study arises from the scientific and clinical significance of examining RBC interaction mechanisms as a model for studying general cell interaction in cytological science. Exploring the phenomenon and mechanism of the photobiomodulation of laser radiation on the rheological properties of RBC has a great potential in the field of laser blood therapy.Interaction dynamics and the role of intercellular interaction time and mutual contact in RBC aggregation and OT-induced disaggregation in autologous plasma are presented as new evidence, clarifying the RBC interaction mechanism. The rheological alterations of RBC induced by laser radiation with various irradiation conditions were thoroughly explored at a single-cell level for the first time to provide a better understanding of the underlying mechanism of photobiomodulation on blood. This study demonstrated the beneficial effects of low-level laser irradiation by a 450-nm wavelength with a radiant exposure below 9.5 J/cm2 of improving RBC deformability and preserving cell shape in a harsh environment. Additionally, irradiated RBC aggregates were easily destroyed by the external influence (i.e., optical force), which could be the flow shearing force in a blood vessel and geometrical resistance by vasculature for in vivo conditions.The current work is important for optimizing the technique of the OT-based RBC evaluation system. It will contribute to the development of effective approaches for improving blood cell viability and blood microcirculation based on the reported photobiomodulation effects.Original papersOriginal papers are not included in the electronic version of the dissertation.Zhu, R., Avsievich, T., Su, X., Bykov, A., Popov, A., & Meglinski, I. (2022). Hemorheological alterations of red blood cells induced by 450-nm and 520-nm laser radiation. Journal of Photochemistry and Photobiology B: Biology, 230, 112438. https://doi.org/10.1016/j.jphotobiol.2022.112438Self-archived versionZhu, R., Avsievich, T., Popov, A., Bykov, A., & Meglinski, I. (2021). In vivo nano-biosensing element of red blood cell-mediated delivery. Biosensors and Bioelectronics, 175, 112845. https://doi.org/10.1016/j.bios.2020.112845Self-archived versionZhu, R., Avsievich, T., Bykov, A., Popov, A., & Meglinski, I. (2019). Influence of pulsed He–Ne laser irradiation on the red blood cell interaction studied by optical tweezers. Micromachines, 10(12), 853. https://doi.org/10.3390/mi10120853Self-archived versionZhu, R., Avsievich, T., Popov, A., & Meglinski, I. (2020). Optical tweezers in studies of red blood cells. Cells, 9(3), 545. https://doi.org/10.3390/cells9030545Self-archived versionZhu, R., Avsievich, T. I., Popov, A., Bykov, A., & Meglinski, I. (2021). In vitro influence of 520 nm diode laser irradiation on red blood cell spontaneous aggregation studied by optical tweezers and light microscopy. Proceedings of SPIE, Optical Trapping and Optical Micromanipulation XVIII 11798, 1179809. https://doi.org/10.1117/12.2595118Self-archived versionZhu, R., Popov, A., & Meglinski, I. (2020). Probing the red blood cell interaction in individual cell pairs by optical tweezers. Conference on Lasers and Electro-optics, AW3I.4. https://doi.org/10.1364/CLEO_AT.2020.AW3I.4Self-archived versionZhu, R., Avsievich, T., Popov, A., & Meglinski, I. (2019). Influence of interaction time on the red blood cell (dis)aggregation dynamics in vitro studied by optical tweezers. Proceedings of SPIE, Novel Biophotonics Techniques and Applications V 11075, 110750D. https://doi.org/10.1117/12.2526778Self-archived versionTiivistelmäTässä opinnäytetyössä raportoidaan ihmisen punasolujen (RBC) perustavanlaatuisen vuorovaikutusdynamiikan tutkimuksista optisilla pinseteillä (OT) ja OT-pohjaisen RBC-tutkimusprotokollan soveltamisesta veren fotobiomodulaatiotutkimuksen helpottamiseksi yksisolutasolla. Motivaatio nykyiselle tutkimukselle syntyy punasolujen vuorovaikutusmekanismien tutkimisen tieteellisestä ja kliinisestä merkityksestä mallina yleisen soluvuorovaikutuksen tutkimiseen sytologiassa. Kun lasersäteilyn fotobiomodulaation ilmiötä ja mekanismia tutkitaan punasolujen reologisissa ominaisuuksissa, siinä on paljon potentiaalia laserveriterapian alalla.Interaktiodynamiikka ja solunvälisen interaktioajan ja keskinäisen kontaktin rooli punasolujen aggregaatiossa ja OT:n aiheuttamassa hajoamisessa autologisessa plasmassa esitetään uutena todisteena punasolujen yhteisvaikutusmekanismia selventävänä näyttönä. Punasoluissa tapahtuneita, lasersäteilyn erilaisissa valaistusolosuhteissa aiheuttamia reologisia muutoksia tarkasteltiin nyt ensimmäistä kertaa perusteellisesti yksittäisten solujen tasolla, minkä seurauksena saatiin aiempaa parempi ymmärrys veren fotobiomodulaation taustalla olevasta mekanismista. Tutkimus havainnollisti matalaenergisen, teholtaan alle 9,5 J/cm2:n säteilyaltistuksen ja aallonpituudeltaan 450 nm:n lasersäteilyn hyödylliset vaikutukset punasolujen muodonmuutoksen parantamisessa ja solujen kyvyssä säilyttää muotonsa ankarissakin olosuhteissa. Lisäksi säteilytetyt RBC-aggregaatit tuhoutuivat helposti ulkoisen vaikutuksen vaikutuksesta (optinen voima), joka voi olla virtauksen leikkausvoima verisuonessa ja geometrinen vastus verisuonissa in vivo -olosuhteissa.Tutkimuksen saavutukset ovat merkittäviä optimoitaessa optiseen pinsettiin perustuvan punasolujen arviointijärjestelmän tekniikoita. Raportoitujen fotobiomodulaatio vaikutusten kautta työ edistää verisolujen elinkelpoisuuden ja veren mikrovirtauksen parantamiseen tähtäävien tehokkaiden lähestymistapojen kehittämistä.OsajulkaisutOsajulkaisut eivät sisälly väitöskirjan elektroniseen versioon.Zhu, R., Avsievich, T., Su, X., Bykov, A., Popov, A., & Meglinski, I. (2022). Hemorheological alterations of red blood cells induced by 450-nm and 520-nm laser radiation. Journal of Photochemistry and Photobiology B: Biology, 230, 112438. https://doi.org/10.1016/j.jphotobiol.2022.112438Rinnakkaistallennettu versioZhu, R., Avsievich, T., Popov, A., Bykov, A., & Meglinski, I. (2021). In vivo nano-biosensing element of red blood cell-mediated delivery. Biosensors and Bioelectronics, 175, 112845. https://doi.org/10.1016/j.bios.2020.112845Rinnakkaistallennettu versioZhu, R., Avsievich, T., Bykov, A., Popov, A., & Meglinski, I. (2019). Influence of pulsed He–Ne laser irradiation on the red blood cell interaction studied by optical tweezers. Micromachines, 10(12), 853. https://doi.org/10.3390/mi10120853Rinnakkaistallennettu versioZhu, R., Avsievich, T., Popov, A., & Meglinski, I. (2020). Optical tweezers in studies of red blood cells. Cells, 9(3), 545. https://doi.org/10.3390/cells9030545Rinnakkaistallennettu versioZhu, R., Avsievich, T. I., Popov, A., Bykov, A., & Meglinski, I. (2021). In vitro influence of 520 nm diode laser irradiation on red blood cell spontaneous aggregation studied by optical tweezers and light microscopy. Proceedings of SPIE, Optical Trapping and Optical Micromanipulation XVIII 11798, 1179809. https://doi.org/10.1117/12.2595118Rinnakkaistallennettu versioZhu, R., Popov, A., & Meglinski, I. (2020). Probing the red blood cell interaction in individual cell pairs by optical tweezers. Conference on Lasers and Electro-optics, AW3I.4. https://doi.org/10.1364/CLEO_AT.2020.AW3I.4Rinnakkaistallennettu versioZhu, R., Avsievich, T., Popov, A., & Meglinski, I. (2019). Influence of interaction time on the red blood cell (dis)aggregation dynamics in vitro studied by optical tweezers. Proceedings of SPIE, Novel Biophotonics Techniques and Applications V 11075, 110750D. https://doi.org/10.1117/12.2526778Rinnakkaistallennettu versioAcademic dissertation to be presented with the assent of the Doctoral Programme Committee of Information Technology and Electrical Engineering of the University of Oulu for public defence in the OP auditorium (L10), Linnanmaa, on 30 June 2022, at 12 noonAbstract
This thesis reports on studies of the fundamental interaction dynamics of human red blood cells (RBC) by optical tweezers (OT) and the application of the OT-based RBC-investigation protocol in facilitating blood photobiomodulation research at a single-cell level. The motivation for the present study arises from the scientific and clinical significance of examining RBC interaction mechanisms as a model for studying general cell interaction in cytological science. Exploring the phenomenon and mechanism of the photobiomodulation of laser radiation on the rheological properties of RBC has a great potential in the field of laser blood therapy.
Interaction dynamics and the role of intercellular interaction time and mutual contact in RBC aggregation and OT-induced disaggregation in autologous plasma are presented as new evidence, clarifying the RBC interaction mechanism. The rheological alterations of RBC induced by laser radiation with various irradiation conditions were thoroughly explored at a single-cell level for the first time to provide a better understanding of the underlying mechanism of photobiomodulation on blood. This study demonstrated the beneficial effects of low-level laser irradiation by a 450-nm wavelength with a radiant exposure below 9.5 J/cm2 of improving RBC deformability and preserving cell shape in a harsh environment. Additionally, irradiated RBC aggregates were easily destroyed by the external influence (i.e., optical force), which could be the flow shearing force in a blood vessel and geometrical resistance by vasculature for in vivo conditions.
The current work is important for optimizing the technique of the OT-based RBC evaluation system. It will contribute to the development of effective approaches for improving blood cell viability and blood microcirculation based on the reported photobiomodulation effects.Tiivistelmä
Tässä opinnäytetyössä raportoidaan ihmisen punasolujen (RBC) perustavanlaatuisen vuorovaikutusdynamiikan tutkimuksista optisilla pinseteillä (OT) ja OT-pohjaisen RBC-tutkimusprotokollan soveltamisesta veren fotobiomodulaatiotutkimuksen helpottamiseksi yksisolutasolla. Motivaatio nykyiselle tutkimukselle syntyy punasolujen vuorovaikutusmekanismien tutkimisen tieteellisestä ja kliinisestä merkityksestä mallina yleisen soluvuorovaikutuksen tutkimiseen sytologiassa. Kun lasersäteilyn fotobiomodulaation ilmiötä ja mekanismia tutkitaan punasolujen reologisissa ominaisuuksissa, siinä on paljon potentiaalia laserveriterapian alalla.
Interaktiodynamiikka ja solunvälisen interaktioajan ja keskinäisen kontaktin rooli punasolujen aggregaatiossa ja OT:n aiheuttamassa hajoamisessa autologisessa plasmassa esitetään uutena todisteena punasolujen yhteisvaikutusmekanismia selventävänä näyttönä. Punasoluissa tapahtuneita, lasersäteilyn erilaisissa valaistusolosuhteissa aiheuttamia reologisia muutoksia tarkasteltiin nyt ensimmäistä kertaa perusteellisesti yksittäisten solujen tasolla, minkä seurauksena saatiin aiempaa parempi ymmärrys veren fotobiomodulaation taustalla olevasta mekanismista. Tutkimus havainnollisti matalaenergisen, teholtaan alle 9,5 J/cm2:n säteilyaltistuksen ja aallonpituudeltaan 450 nm:n lasersäteilyn hyödylliset vaikutukset punasolujen muodonmuutoksen parantamisessa ja solujen kyvyssä säilyttää muotonsa ankarissakin olosuhteissa. Lisäksi säteilytetyt RBC-aggregaatit tuhoutuivat helposti ulkoisen vaikutuksen vaikutuksesta (optinen voima), joka voi olla virtauksen leikkausvoima verisuonessa ja geometrinen vastus verisuonissa in vivo -olosuhteissa.
Tutkimuksen saavutukset ovat merkittäviä optimoitaessa optiseen pinsettiin perustuvan punasolujen arviointijärjestelmän tekniikoita. Raportoitujen fotobiomodulaatio vaikutusten kautta työ edistää verisolujen elinkelpoisuuden ja veren mikrovirtauksen parantamiseen tähtäävien tehokkaiden lähestymistapojen kehittämistä
SHOCK THERAPY VERSUS GRADUALISM RECONSIDERED: LESSONS FROM TRANSITION ECONOMIES AFTER 15 YEARS OF REFORMS
Get PDFThis paper starts by separating the transformational recession (reduction of output in most transition economies in the first half of the 1990s) from the process of economic growth (recovery from the transformational recession) in 28 transition economies (including China,Vietnam and Mongolia). It is argued that the former (the collapse of output during transition) can be best explained as adverse supply shock caused mostly by a change in relative prices after their deregulation due to distortions in industrial structure and trade patterns accumulated during the period of central planning, and by the collapse of state institutions during transition period, while the speed of liberalization, to the extent it was endogenous, i.e. determined by political economy factors, had an adverse effect on performance. In contrast, at the recovery stage the ongoing liberalization starts to affect growth positively, whereas the impact of pre-transition distortions disappears. Institutional capacity and reasonable macroeconomic policy, however, continue to be important prerequisites for successful performance.
A Popov criterion for networked systems
No full textWe consider robustness analysis of heterogeneous and homogeneous networked systems based on integral quadratic constraints (IQCs). First, we show how the analysis decomposes into lower dimensional problems if the interconnection structure is exploited. This generally leads to a significant reduction of the computational complexity. Secondly, by considering a set of IQCs that characterizes the eigenvalues of the interconnection matrices of symmetrically networked systems, we derive a Popov-like criterion for such systems. In particular, when the nodes of the networked system are single-input-single-output linear time-invariant operators, the criterion can be illustrated using a generalized Popov plot. In such cases. the Popov criterion is also a necessary condition in the sense that if the criterion is violated then a destabilizing network with the specified eigenvalue distribution can be constructed.</p
Development and Use of Dried Plasma Spots Technique for Quantitative Determination of Topiramate in Pharmacokinetics and Bioequivalence Studies
Get PDFV okviru doktorskega dela sem razvila in ovrednotila tehniko suhe lise plazme za kvantitativno določevanje topiramata v študijah farmakokinetike in bioekvivalence. Tehnika suhe lise plazme je izpeljana iz tehnike suhe lise krvi. Slednjo so v zadnjih dveh letih bioanalitiki, farmakokinetiki in klinični raziskovalci na novo odkrili in jo uvedli v študije farmakokinetike in bioekvivalence kot alternativo za tradicionalno vzorčenje in določevanje učinkovin iz tekoče humane plazme.
Tehnika odvzema vzorcev krvi na papir, znana kot suha lisa krvi (v nadaljevanju DBS – Dried Blood Spots), se je začela uporabljati v zgodnjih šestdesetih letih prejšnjega stoletja v presejalnih testih za novorojenčke. Danes pri izvajanju farmakokinetičnih in bioekvivalenčnih študijah DBS nudi v primerjavi z običajno plazmo veliko prednosti, ki se nanašajo na praktične, etične in stroškovne aspekte. DBS omogoča manj invazivno vzorčenje (vbod v prst ali peto namesto uporabe običajne venske kanile) in etične prednosti odvzema manjšega volumna krvi (manj kot 100 µL v primerjavi z več kot 1,0 mL krvi pri običajnem vzorčenju krvi). Poleg tega omogoča lažji transport in enostavnejše ter cenejše shranjevanje (ni potrebe po suhem ledu ali zamrzovalnikih).
V obdobju obujanja DBS tehnike so se obravnavala predvsem vprašanja iz vidika njenih praktičnih prednosti, tehničnih izboljšav ter morebitnih analiznih težav in so ji šele pozneje namenili pozornost s stališča farmakokinetike in farmakodinamike. Tedaj so ugotovili, da matrica krvi in s tem DBS tehnika ni primerna za določevanje zdravilnih učinkovin v vseh vrstah študij. DBS tehnika tako še ni regulatorno priznana kot samostojna metoda za kvantitativno določevanje zdravilnih učinkovin pri registraciji humanih in veterinarskih zdravil.
Pri farmakokinetičnih študijah običajno kot biološko matrico za določevanje zdravilnih učinkovin uporabljamo tekočo plazmo. Zgoraj omenjena tehnika suhe lise plazme (v nadaljevanju DPS – Dried Plasma Spots) nudi enake prednosti kot DBS tehnika, poleg tega pa je plazma že uveljavljena biološka matrica za analizo večine zdravilnih učinkovin. Pri tem se mi je porajalo vprašanje, ali lahko tehnika suhe lise plazme popolnoma zamenja klasično metodo določevanja zdravilnih učinkovin iz temeljne matrice, tekoče plazme.
Odgovor sem iskala na primeru spojine topiramat. Topiramat (TPM) je antiepileptično zdravilo, ki ga uporabljamo za zdravljenje različnih vrst epilepsije pri odraslih in otrocih, za preprečevanje pogosto ponavljajočih se napadov migrene pri odraslih ter kot dodatno zdravilo za zdravljenje Lennox-Gastautovega sindroma. Topiramat spodbuja delovanje inhibitornih nevrotransmiterjev (GABA), blokira Na-kanale in šibko inhibira karbonsko anhidrazo. Vezava na karboanhidrazo, ki je v veliki meri prisotna v eritrocitih, pa lahko vpliva na farmakokinetiko zdravilne učinkovine. Topiramat ima tendenco vezave na karboanhidrazo v eritrocitih, kar pomeni, da se koncentracije v krvi v odvisnosti od časa lahko razlikujejo od plazemskega profila, ter da je razmerje koncentracij kri - plazma večje od 1.
Namen raziskave je bil na podlagi literature, DBS ter DPS vzorcev študije spremljanja terapevtskega učinka oceniti, katera suha biološka matrica je najprimernejša za njegovo kvantitativno določevanje v bioloških vzorcih študij farmakokinetike in bioekvivalence.
Doktorska naloga je sestavljena iz treh raziskav. Razvila in preizkusila sem tri bioanalizne metode za določevanje topiramata v bioloških matricah. V prvi fazi sem razvila in preizkusila metodo za kvantitativno določevanje topiramata iz suhe lise plazme. V drugem in tretjem delu raziskave sem razvila in preizkusila metodo iz tekoče humane plazme ter metodo določevanja topiramata iz suhe lise krvi. Za kvantitativno določitev koncentracij topiramata sem uporabila metodo devteriranega internega standarda (topiramat-d12) in tekočinsko kromatografijo s tandemskim masnim spektrometrom. Spojine sem ionizirala z elektrorazprševanjem (ESI) in doloIn my doctoral studies I have developed and evaluated dried plasma spot technique for determining topiramate in pharmacokinetic and bioequivalence studies. Dried plasma spot technique derives from dried blood spot technique. In the last two years the latter was rediscovered by bioanalysts and pharmacokineticians and introduced in pharmacokinetic and bioequivalence studies as an alternative for traditional sampling and determination of substances from liquid human plasma.
The collection of whole blood samples on paper, known as the dried blood spot technique (DBS), dates back to the early 1960s, when it was used for detecting metabolic problems in newborns. Today DBS offers a number of advantages over the conventional whole blood in pharmacokinetic and bioequivalence studies. These advantages are related to ethical, practical, and cost aspects. DBS provides the ethical benefits of reduced blood volume (less than 100 μL compared to more than 1.0 mL blood, which is usually obtained during the conventional blood sample collection) and less invasive sampling (finger or heel prick rather than conventional venous cannula). Furthermore, it provides easier transfer and simpler and cheaper storage (no need for dry ice or freezers).
When DBS technique was being reintroduced, the questions from the perspective of its practical advantages, technical improvements and possible analysis problems were considered. It was only until later that the technique got attention from the viewpoint of pharmacokinetics and bioanalysis. At that point it was discovered that blood matrix and consequently DBS technique is not useful for determining active substances in all types of studies. Therefore, DBS technique hasn’t been regulatory acknowledged as an independent method for the quantitative determination of active substances when it comes to the registration of human and veterinary drugs.
In pharmacokinetic studies, liquid plasma is usually used as biological matrix for the determination of active substances. The aforementioned dried plasma spot technique (from now on DPS – Dried Plasma Spot) offers the same advantages as DBS technique alongside with the advantage of plasma being already an acknowledged matrix for the majority of active substances. As a result, I considered, a question whether DPS technique can completely replace the method of determining active substances from the basic matrix, liquid plasma.
The answer to that question was sought on the case of the compound topiramate. Topiramate is an anti-epileptic drug that is used for the treatment of various forms of epilepsy in adults and children and for the prevention of frequently recurring migraines in adults as well as for the treatment of Lennox-Gastaut syndrome. Topiramate enhances the action of inhibitory neurotransmitters (GABA), blocks voltage-sensitive sodium channels and mildly inhibits carbonic anhydrase (CA) isoenzymes. Binding to CA, which is highly concentrated in erythrocytes, may affect drug pharmacokinetics. Topiramate’s tendency to bind to CA in erythrocytes implies that blood concentration-time profile may be different from plasma profile and the blood-to-plasma ratio might be greater than 1.
The purpose of the research was to determine which is the most appropriate dried matrix for the quantitative determination of topiramate in biological samples of pharmacokinetic and bioequivalence studies, on the basis of literature and DBS and DPS samples from the monitoring research on the therapeutic effect.
The doctoral dissertation consists of three parts of experimental work. In the first part, the method for quantitative determination of topiramate from dried plasma spot was developed and validated. In the second and third part of the experimental work, the method for quantitative determination of topiramate from liquid human plasma and the method for quantitative determination of topiramate from dried blood spot were developed and validated. For quantitative determination of TPM concentration the method with deuterated internal standard (topiramate-d12) an
Metoisops grabenhorsti Herczek & Popov, sp. nov.
No full text<i>Metoisops grabenhorsti</i> Herczek & Popov, sp. nov. <p>(Figs. 18–19)</p> <p> <b>Diagnosis.</b> This species is clearly different from other species in this genus by very broad vertex and also broad visible portion of the mesoscutum.</p> <p> <b>Description.</b> Body 2.66 mm, elongate, 2.4x as long as wide. General coloration uniformly dark-brown, especially pronotum and mesoscutum; scutellum pale yellow. Hemelytra covered with dense, relatively short, adpressed golden hairs arising from articulate punctures; outer margin of hemelytra distinctly polished and inpunctate; scutellum shiny with same pale hairs at the base (Figs. 18, 19). Head moderately transverse, 2.61x as wide as long, distinctly wider than anterior margin of pronotum. Vertex quite wide, dorsal width of eye only 1.43x wider than width v e r t e x; eyes globular. 2nd antennal segment 3 times longer than 1st. Pronotum trapezoidal, moderately transversal, 1.72x as wide as long; calli weakly developed, intercallian pit weakly expressed; ratio length posterior/anterior margin 2.4x wider than median length; posterior margin weakly convex. Visible portion of mesoscutum v e r y narrow exposed, length scutellum 4.35x longer. Claval commissura long, ratio length claval commissure/mesoscutum+scutellum 1.2. Corium length 4.7x longer than cuneus; cuneus twice as long as wide; large cell of hemelytral membrane long, 3.2x as long as wide. Tibia 2.8x longer than tarsus; 1st tarsal segment of hind leg 1.77x shorter than 2nd one.</p> <p> <b>Dimensions</b>. Male. Length of body from apex of hemelytra 2.66, width 1.1; length of head 0.18, width 0.47, dorsal width of eye 0.26, width of vertex 0.18; antennal segments I:II = 0.23:0.72, III, IV–invisibly; rostral segments I 0.28, II, III, IV–invisibly; length of pronotum 0.36 (max.), width 0.26 (ant.) and 0.62 (post.); length of mesoscutum 0.1; length of scutellum 0.26; claval commissure 0.49; length of hind femur 0.83; length of tibia 0.95; length of tarsus 0.34 (I+II = 0.13+0.23).</p> <p> <b>Etymology.</b> This species is named after Mr. Heirich Grabenhorst (Hamburg, Germany), who acquired this amber piece for his collection, provided the specimen for scientific study and generously donated the type material to the GPIMH.</p> <p> <b>Specimens examined.</b> Holotype, ♂, in Baltic amber (coll. H. Grabenhorst, Het-7) light reddish and smallsized piece of amber (10 x 7 mm) of irregular shape, which embedded into artificial resin (35 x 15 mm). The holotype is deposited in the collection of GPIMH.</p> <p> <b>Remarks.</b> <i>M. grabenhorsti</i> shares features in common with other species in the genus such as the ratio width/ length pronotum (1.72–1.82) that is similar to <i>M. punctatus, M. intergerivus, M. variabilis</i> and <i>M. punctatodiffusus</i>, and also ratio length posterior/anterior margin of pronotum (2.3–2.4x wider than long). However this species is clearly different from all species by very broad vertex (only 1.43x narrower than eye) and also very broad visible portion of mesoscutum (approximately 2.6x shorter than scutellum length) and ratio length claval commissure/ mesoscutum+scutellum (1.2).</p>Published as part of <i>Herczek, Aleksander & Popov, Yuri A., 2014, Revision of the genus Metoisops (Hemiptera: Heteroptera, Miridae, Isometopinae) from late Eocene European amber, pp. 401-421 in Zootaxa 3887 (3)</i> on pages 415-417, DOI: 10.11646/zootaxa.3887.4.1, <a href="http://zenodo.org/record/251002">http://zenodo.org/record/251002</a>
Metoisops punctatodiffusus Herczek & Popov, sp. nov.
No full textMetoisops punctatodiffusus Herczek & Popov, sp. nov. (Figs. 16–17) Diagnosis. This species is clearly different from all species by very broad open part of mesoscutum, the ratio length claval commissure/ mesoscutum+scutellum, and also scattered punctate of hemelytra. Description. Body elongate, 2.4 mm long; body, 2.32 x as long as wide. General coloration yellow, head, pronotum and mesonotum dark yellow, scutellum white. Head and scutellum bare, pronotum and hemelytra with scattered punctuation, with reclining pale short hairs arising from articulate punctures; scutellum shiny, inpunctate; outer margin of hemelytra distinctly polish and inpunctate; cuneus semi-transparence, inpunctate (Figs. 16, 17). Head moderately transverse, 2. 5 x as wide as long, wider than anterior margin of pronotum. Vertex 1.55 x narrower than dorsal width of eye; eyes globular; combined antennal length of 3 rd and 4 t h segments equal in length and width, 3 rd segment 1.16 x longer than 4 th; ratio length 2 nd– 1 st and 4 th– 3 rd rostral segments 1.12, 4th segment shortest. Pronotum trapezoidal, moderately transversal, 1.79 x as wide as long; calli weakly developed, intercallian pit poorly developed; ratio length posterior/anterior margin 2.1 x; posterior margin weakly convex in middle. Visible portion of mesoscutum 1.77 x shorter than scutellum length. Claval commissura long, ratio length claval commissure/mesoscutum+scutellum 1.67. Corium length 4.8 x longer than cuneus. Cuneus twice as long as wide and 1.6 x as long as wide; large cell of hemelytral membrane very long, 5 x as long as wide. Hind femur nearly reaching apex of abdomen, rather thickened, approximately 5.35 x longer than width and 1.31 x shorter than tibia; tibia 3.53 x longer than tarsus; 2 nd tarsal segment of hind leg 1.77 x longer than 1 st. Dimensions. Length of body 2.4, width 1.1; length of head 0.26, width 0.65, dorsal width of eye 0.26, width of vertex 0.16; antennal segments I:II:III:IV= 0.23: 0.66: 0.36: 0.31; rostral segments I:II:III:IV= 0.34: 0.38: 0.25: 0.28; length of pronotum 0.53, width 0.45 (ant.) and 0.95 (post.); length of mesoscutum 0.13; length of scutellum 0.23; claval commissure 052; length of hind femur 0.91, width 0.17; length of tibia 1.20; length of tarsus 0.34 (I+II = 0.13 + 0.23). Etymology. From punctum (lat.) = dot and diffuses (lat.) = dispersed. Specimens examined. Holotype, ♂, in Baltic amber PIN RAS 964 / 1309 Remarks. M. punctatodiffusus and M. intergerivus share the characteristic of the shiny inpunctate, practically bare scutellum. M. punctatodiffusus can be differentiated by very broad open part of scutellum (approximately 1.8 x shorter than scutellum length), ratio length claval commissure/mesoscutum+scutellum (1.44) and the scattered punctuation on the hemelytra.Published as part of Herczek, Aleksander & Popov, Yuri A., 2014, Revision of the genus Metoisops (Hemiptera: Heteroptera, Miridae, Isometopinae) from late Eocene European amber, pp. 401-421 in Zootaxa 3887 (3) on page 415, DOI: 10.11646/zootaxa.3887.4.1, http://zenodo.org/record/25100
Metoisops intergerivus Herczek & Popov, sp. nov.
No full textMetoisops intergerivus Herczek & Popov, sp. nov. (Figs. 14–15) Diagnosis. This species is characterized by moderate punctuation of hemelytra, dark cuneal apex and shiny, practically bare scutellum. Description. Body elongate, 2.5 x as long as wide. General coloration uniform reddish-brown, apex of cuneus dark. Head bare; corium, cuneus and clavus furnish with golden yellow adpressed setae, pronotum and scutellum scattered short setae. Hemelytra with moderately punctate corium and clavus, moderately pubescent with reclining golden-yellow short setae arising from articulate punctures; cuneus semi-transparence, inpunctate (Figs. 14, 15). Head moderately transverse, 2.36 x as wide as long, distinctly wider than anterior margin of pronotum. Vertex 1.64 x narrower than dorsal width of eye; eyes globular; combined antennal length of 3 rd and 4 t h segments 1.1 x longer than 2 nd, 2 nd segment 3.36 x longer than 1 st; 4 th segment 1.33 x longer than 3 rd. 4 th antennal segment sometimes subdivided into 2 parts; 2 nd and 3 rd rostral segments equal size in width and length, 2 nd segment twice as longer as 1 st. 3 rd segment 0.91 x longer than 4 rd. Pronotum trapezoidal in shape, moderately transversal, 1.82 x as wide as long; calli weakly developed, intercallian pit weakly expressed; ratio length posterior/anterior margin 2.23 x wider than median length; posterior margin weakly convex. Visible portion of mesoscutum narrowly exposed, 4.0x shorter than scutellum length. Claval commissura rather long, ratio length claval commissure/mesoscutum+scutellum 1.25. Cuneus 4.8 x shorter in length than length of corium and twice as long as wide; large cell of hemelytral membrane very long, 4.0x as long as wide. Hind tibia 3.64 x longer than tarsus; 1 st tarsal segment of hind leg very short; 2 nd segment 2.77 x longer than 1 st. Dimensions. Length of body 2.74, width 1.1; length of head 0.25, width 0.63, dorsal width of eye 0.23, width of vertex 0.14; antennal segments I:II:III:IV= 0.25: 0.84: 0.39: 0.52; rostral segments I:II:III:IV= 0.18: 0.36:0: 36:0: 33; length of pronotum 0.52, width 0.43 (ant.) and 0.95 (post.); length of mesoscutum 0.1; length of scutellum 0.40; claval commissure 0.5; hind femur–invisibly; length of tibia 1.24; length of tarsus 0.34 (I+II = 0.09 + 0.25). Etymology. From intergerivus (lat.) = placed between. Specimens Examined. Holotype, ♂, in Baltic amber (coll. C. Gröhn Nr. 2291) light yellowish and moderatesized piece of amber (29 x 18 mm) of irregular shape. The holotype is deposited in the collection of GPIMH. Remarks. M. intergerivus shares in such features as ratio width/length pronotum (1,72– 1.82) with M. punctatus, M. grabenhorsti, M. variabilis, and M. punctatodiffusus, narrow open part of mesoscutum in M. punctatus, M. variabilis. M. groehni and M. akingbohungbei, and also ratio length claval commissure/ mesoscutum+scutellum (1.2–1.27) in most species (except M. akingbohungbei). M. variabilis has also a very long large cell in hemelytral membrane (3.8 –4.0 x as long as wide).Published as part of Herczek, Aleksander & Popov, Yuri A., 2014, Revision of the genus Metoisops (Hemiptera: Heteroptera, Miridae, Isometopinae) from late Eocene European amber, pp. 401-421 in Zootaxa 3887 (3) on pages 412-414, DOI: 10.11646/zootaxa.3887.4.1, http://zenodo.org/record/25100
KYP lemma based stability and control law design for differential linear repetitive processes with applications
No full textRepetitive processes are a class of two-dimensional systems that have physical applications, including the design of iterative learning control laws where experimental validation results have been reported. This paper uses the Kalman–Yakubovich–Popov lemma to develop new stability tests for differential linear repetitive processes that are computationally less intensive than those currently available. These tests are then extended to allow control law design for stability and performance
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