Transfer entropy reconstruction and labeling of neuronal connections from simulated calcium imaging

Neuronal dynamics are fundamentally constrained by the underlying structural network architecture, yet much of the details of this synaptic connectivity are still unknown even in neuronal cultures in vitro. Here we extend a previous approach based on information theory, the Generalized Transfer Entropy, to the reconstruction of connectivity of simulated neuronal networks of both excitatory and inhibitory neurons. We show that, due to the model-free nature of the developed measure, both kinds of connections can be reliably inferred if the average firing rate between synchronous burst events exceeds a small minimum frequency. Furthermore, we suggest, based on systematic simulations, that even lower spontaneous inter-burst rates could be raised to meet the requirements of our reconstruction algorithm by applying a weak spatially homogeneous stimulation to the entire network. By combining multiple recordings of the same in silico network before and after pharmacologically blocking inhibitory synaptic transmission, we show then how it becomes possible to infer with high confidence the excitatory or inhibitory nature of each individual neuron.

Reliability of the density functional approximation to describe the charge transfer and electrostatic complexes involved in the modeling of organic conducting polymers

Both the intermolecular interaction energies and the geometries for M ̄ thiophene, M ̄ pyrrole, M n+ ̄ thiophene, and M n+ ̄ pyrrole ͑with M = Li, Na, K, Ca, and Mg; and M n+ = Li+ , Na+ , K+ , Ca2+, and Mg2+͒ have been estimated using four commonly used density functional theory ͑DFT͒ methods: B3LYP, B3PW91, PBE, and MPW1PW91. Results have been compared to those provided by HF, MP2, and MP4 conventional ab initio methods. The PBE and MPW1PW91 are the only DFT methods able to provide a reasonable description of the M ̄ complexes. Regarding M n+ ̄ ␲ complexes, the four DFT methods have been proven to be adequate in the prediction of these electrostatically stabilized systems, even though they tend to overestimate the interaction energies.

TGF-β dependent regulation of oxygen radicals during transdifferentiation of activated hepatic stellate cells to myofibroblastoid cells

Background: The activation of hepatic stellate cells (HSCs) plays a pivotal role during liver injury because the resulting myofibroblasts (MFBs) are mainly responsible for connective tissue re-assembly. MFBs represent therefore cellular targets for anti-fibrotic therapy. In this study, we employed activated HSCs, termed M1-4HSCs, whose transdifferentiation to myofibroblastoid cells (named M-HTs) depends on transforming growth factor (TGF)-β. We analyzed the oxidative stress induced by TGF-β and examined cellular defense mechanisms upon transdifferentiation of HSCs to M-HTs. Results: We found reactive oxygen species (ROS) significantly upregulated in M1-4HSCs within 72 hours of TGF-β administration. In contrast, M-HTs harbored lower intracellular ROS content than M1-4HSCs, despite of elevated NADPH oxidase activity. These observations indicated an upregulation of cellular defense mechanisms in order to protect cells from harmful consequences caused by oxidative stress. In line with this hypothesis, superoxide dismutase activation provided the resistance to augmented radical production in M-HTs, and glutathione rather than catalase was responsible for intracellular hydrogen peroxide removal. Finally, the TGF-β/NADPH oxidase mediated ROS production correlated with the upregulation of AP-1 as well as platelet-derived growth factor receptor subunits, which points to important contributions in establishing antioxidant defense. Conclusion: The data provide evidence that TGF-β induces NADPH oxidase activity which causes radical production upon the transdifferentiation of activated HSCs to M-HTs. Myofibroblastoid cells are equipped with high levels of superoxide dismutase activity as well as glutathione to counterbalance NADPH oxidase dependent oxidative stress and to avoid cellular damage.

Anomalous optical and electrical recovery process of photoquenched EL2 defect produced by oxygen and boron ion implantation in gallium arsenide

The optical and electrical recovery processes of the metastable state of the EL2 defect artificially created in n‐type GaAs by boron or oxygen implantation are analyzed at 80 K using optical isothermal transient spectroscopy. In both cases, we have found an inhibition of the electrical recovery and the existence of an optical recovery in the range 1.1-1.4 eV, competing with the photoquenching effect. The similar results obtained with both elements and the different behavior observed in comparison with the native EL2 defect has been related to the network damage produced by the implantation process. From the different behavior with the technological process, it can be deduced that the electrical and optical anomalies have a different origin. The electrical inhibition is due to the existence of an interaction between the EL2 defect and other implantation‐created defects. However, the optical recovery seems to be related to a change in the microscopic metastable state configuration involving the presence of vacancies

Horizontal transfer of exosomal microRNAs transduce apoptotic signals between pancreatic beta-cells.

BACKGROUND: Diabetes mellitus is a common metabolic disorder characterized by dysfunction of insulin-secreting pancreatic beta-cells. MicroRNAs are important regulators of beta-cell activities. These non-coding RNAs have recently been discovered to exert their effects not only inside the cell producing them but, upon exosome-mediated transfer, also in other recipient cells. This novel communication mode remains unexplored in pancreatic beta-cells. In the present study, the microRNA content of exosomes released by beta-cells in physiological and physiopathological conditions was analyzed and the biological impact of their transfer to recipient cells investigated. RESULTS: Exosomes were isolated from the culture media of MIN6B1 and INS-1 derived 832/13 beta-cell lines and from mice, rat or human islets. Global profiling revealed that the microRNAs released in MIN6B1 exosomes do not simply reflect the content of the cells of origin. Indeed, while a subset of microRNAs was preferentially released in exosomes others were selectively retained in the cells. Moreover, exposure of MIN6B1 cells to inflammatory cytokines changed the release of several microRNAs. The dynamics of microRNA secretion and their potential transfer to recipient cells were next investigated. As a proof-of-concept, we demonstrate that if cel-miR-238, a C. Elegans microRNA not present in mammalian cells, is expressed in MIN6B1 cells a fraction of it is released in exosomes and is transferred to recipient beta-cells. Furthermore, incubation of untreated MIN6B1 or mice islet cells in the presence of microRNA-containing exosomes isolated from the culture media of cytokine-treated MIN6B1 cells triggers apoptosis of recipient cells. In contrast, exosomes originating from cells not exposed to cytokines have no impact on cell survival. Apoptosis induced by exosomes produced by cytokine-treated cells was prevented by down-regulation of the microRNA-mediating silencing protein Ago2 in recipient cells, suggesting that the effect is mediated by the non-coding RNAs. CONCLUSIONS: Taken together, our results suggest that beta-cells secrete microRNAs that can be transferred to neighboring beta-cells. Exposure of donor cells to pathophysiological conditions commonly associated with diabetes modifies the release of microRNAs and affects survival of recipient beta-cells. Our results support the concept that exosomal microRNAs transfer constitutes a novel cell-to-cell communication mechanism regulating the activity of pancreatic beta-cells.

PPAR-β/δ activation promotes phospholipid transfer protein expression.

The peroxisome proliferator-activated receptor (PPAR)-β/δ has emerged as a promising therapeutic target for treating dyslipidemia, including beneficial effects on HDL cholesterol (HDL-C). In the current study, we determined the effects of the PPAR-β/δ agonist GW0742 on HDL composition and the expression of liver HDL-related genes in mice and cultured human cells. The experiments were carried out in C57BL/6 wild-type, LDL receptor (LDLR)-deficient mice and PPAR-β/δ-deficient mice treated with GW0742 (10mg/kg/day) or a vehicle solution for 14 days. GW0742 upregulated liver phospholipid transfer protein (Pltp) gene expression and increased serum PLTP activity in mice. When given to wild-type mice, GW0742 significantly increased serum HDL-C and HDL phospholipids; GW0742 also raised serum potential to generate preβ-HDL formation. The GW0742-mediated effects on liver Pltp expression and serum enzyme activity were completely abolished in PPAR-β/δ-deficient mice. GW0742 also stimulated PLTP mRNA expression in mouse J774 macrophages, differentiated human THP-1 macrophages and human hepatoma Huh7. Collectively, our findings demonstrate a common transcriptional upregulation by GW0742-activated PPAR-β/δ of Pltp expression in cultured cells and in mouse liver resulting in enhanced serum PLTP activity. Our results also indicate that PPAR-β/δ activation may modulate PLTP-mediated preβ-HDL formation and macrophage cholesterol efflux.

Prediction of heat transfer on kraft recovery boiler

Työssä tutkittiin Andritz-Ahlstrom toimittamien soodakattiloiden lämmönsiirtoa ANITA 2.20- suunnitteluohjelmalla feedback- laskentaa apuna käyttäen. Data laskentaan saatiin kattiloiden takuukokeissa mitatuista arvoista. Mittaukset on suoritettiin Andritz-Ahlstromin henkilökunnan toimesta tehdashenkilökunnan avustuksella. Feedback -laskenta tapahtui mittaustulosten perusteella, joten tiettyä virhettä luonnollisesti esiintyi. Aluksi laskettiin taseet molempien ekojen yli erikseen sekä molemmat yhdessä Excel-taulukkolaskentaohjelmalla. Täältä saatiin oletettu savukaasuvirtaus kattilassa. Tämän jälkeen lämpöpintoja muokattiin todellisuutta vastaaviksi yleislikaisuuskerrointa muuttamalla (overall fouling factor). Kertoimet ovat liikkuivat noin 0.4 ja 1.6 välillä riipuen kattilan tyypistä ja ANITAn oletuksesta lämpöpintojen likaisuudelle. Havaittin että yhtä varsinaista syytä lämpöpintojen eroavaisuuteen oletetusta ei saatu. Syitä toiminnan poikkeamiseen oli monia. Mm. etukammion koolla havaittiin olevan suurtakin vaikutusta tulistimien, etenkin savukaasuvirrassa ensimmäisen tulistimen toimintaan. Yleisesti todettiin muiden tulistimien vastaavan oletettua toimintaa. Keittopinnan ja ekonomiserien toimintaa tutkittiin hivenen suppeammin ja havaittiin niiden toimivan huomattavasti stabiilimmin kuin tulistimien. Likaisuus kertoimet oletetusta vaihtelivat noin ±20 %.

Transfer pricing tool development process based on valve package production costs

Tämän diplomityön päätavoitteena oli parantaa kehitetyn kustannusperusteisen siirtohinnoittelutyökalun ominaisuuksia osastokohtaisen kustannusarviointiprosessin käyttöön. Työ on vaikeutunut lähimenneisyyden heikosta hintakyselyiden vastauskyvystä. Työn pääongelmana oli kerätä luotettavaa tuotannonohjausjärjestelmän kustannusaineistoa osittain vanhentuneista vakioventtiilien koneistus- ja materiaalitiedosta. Tutkimuksessa käytetyt tärkeimmät tutkimusmenetelmät voidaan jakaa siirtohinnoittelu- ja kustannusarvioprosessien kirjallisuustutkimukseen, kenttäanalyysiin ja nykyisen Microsoft Excel –siirtohinnoittelutyökalun kehittämiseen eri osastojen rajapinnassa. Siirtohinnoittelumenetelmät ovat yleisesti jaettu kustannus-, markkina- ja neuvotteluperusteisiin malleihin, jotka harvoin sellaisenaan kohtaavat siirtohinnoittelulle asetetut tavoitteet. Tämä ratkaisutapa voi johtaa tilanteisiin, jossa kaksi erillistä menetelmää sulautuvat yhteen. Lisäksi varsinaiseen siirtohinnoittelujärjestelmään yleensä vaikuttavat useat sisäiset ja ulkoiset tekijät. Lopullinen siirtohinnoittelumenetelmä tulisi ehdottomasti tukea myös yrityksen visiota ja muita liiketoiminnalle asetettuja strategioita. Työn tuloksena saatiin laajennettu Microsoft Excel –sovellus, joka vaatii sekä vuosittaista että kuukausittaista erikoisventtiilimateriaalien hinta- ja toimitusaikatietojen päivittämistä. Tämä ratkaisutapa ehdottomasti parantaa kustannusarviointiprosessia, koska myös alihankkijatietoja joudutaan tutkimaan systemaattisesti. Tämän jälkeen koko siirtohinnoitteluprosessia voidaan kehittää muuntamalla kokoonpano- ja testaustyövaiheiden kustannusrakennetta toimintoperustaisen kustannuslaskentamallin mukaiseksi.

Biogeochemical processes controlling oxygen and carbon isotopes of diatom silica in Late Glacial to Holocene lacustrine rhythmites

Biogeochemical cycles and sedimentary records in lakes are related to climate controls on hydrology and catchment processes. Changes in the isotopic imposition of the diatom frustules (δ 18 O diatom and δ 13 C diatom ) in lacustrine sediments can be used to reconstruct palaeoclimatic and palaeoenvironmental changes. The Lago Chungará (Andean Altiplano, 18°15 ′ S, 69°10 ′ W, 4520 masl) diatomaceous laminated sediments are made up of white and green multiannual rhythmites. White laminae were formed during short-term diatom super-blooms, and are composed almost exclusively of large-sized Cyclostephanos andinus.These diatoms bloom during mixing events when recycled nutrients from the bottom waters are brought to the surface and/or when nutrients are introduced from the catchment during periods of strong runoff. Conversely, the green laminae are thought to have been deposited over several years and are composed of a mixture of diatoms (mainly smaller valves of C. andinus and Discostella stelligera ) and organic matter. These green laminae reflect the lake's hydrological recovery from a status favouring the diatom super-blooms (white laminae) towards baseline conditions. δ 18 O diatom and δ 13 C diatom from 11,990 to 11,530 cal years BP allow us to reconstruct shifts in the precipitation/evaporation ratio and changes in the lake water dissolved carbon concentration, respectively. δ 18 O diatom values indicate that white laminae formation occurred mainly during low lake level stages, whereas green laminae formation generally occurred during high lake level stages. The isotope and chronostratigraphical data together suggest that white laminae deposition is caused by extraordinary environmental events. El Niño-Southern Oscillation and changes in solar activity are the most likely climate forcing mechanisms that could trigger such events, favouring hydrological changes at interannual-to-decadal scale. This study demonstrates the potential for laminated lake sediments to document extreme pluriannual events.

Acetylation of cell wall is required for structural integrity of the leaf surface and exerts a global impact on plant stress responses.

The epidermis on leaves protects plants from pathogen invasion and provides a waterproof barrier. It consists of a layer of cells that is surrounded by thick cell walls, which are partially impregnated by highly hydrophobic cuticular components. We show that the Arabidopsis T-DNA insertion mutants of REDUCED WALL ACETYLATION 2 (rwa2), previously identified as having reduced O-acetylation of both pectins and hemicelluloses, exhibit pleiotrophic phenotype on the leaf surface. The cuticle layer appeared diffused and was significantly thicker and underneath cell wall layer was interspersed with electron-dense deposits. A large number of trichomes were collapsed and surface permeability of the leaves was enhanced in rwa2 as compared to the wild type. A massive reprogramming of the transcriptome was observed in rwa2 as compared to the wild type, including a coordinated up-regulation of genes involved in responses to abiotic stress, particularly detoxification of reactive oxygen species and defense against microbial pathogens (e.g., lipid transfer proteins, peroxidases). In accordance, peroxidase activities were found to be elevated in rwa2 as compared to the wild type. These results indicate that cell wall acetylation is essential for maintaining the structural integrity of leaf epidermis, and that reduction of cell wall acetylation leads to global stress responses in Arabidopsis.

Oxygen adsorption on clean and oxygen precovered Cu(100)

Kuparipinnan hapettumisen alkuvaiheet ovat vielä nykyisin tutkijoille epäselviä. Kuitenkin, jotta hapettumisprosessia voitaisiin säädellä, on sangen tärkeää ymmärtää mistä varsinainen hapettuminen lähtee liikkeelle ja mitkä ovat hapettumisen seuraavat vaiheet. Tähän kysymykseen haetaan vastauksia tässä työssä käyttäen puhtaasti teoreettisia menetelmiä pinnan käsittelyssä. Aikaisempien teoreettisten ja kokeellisten tutkimusten välillä on pieni ristiriita liittyen hapen tarttumistodennäköisyyteen. Teoreettisten tutkimusten mukaan happi ei puhtaalle pinnalle tullessaan näe potentiaalivallia, mutta kokeelliset tutkimukset osoittavat sellaisen kuitenkin olevan. Tuohon ristiriitaan pureudutaan käyttäen aikaisemmista laskuista poikkeavaa kvanttimekaaniseen molekyylidynamiikkaan perustuvaa lähestymistapaa. Työssä havaitaan, että aikaisemmin yleisesti käytetty menetelmä hukkaa huomattavan määrän tietoa ja siten tutkijat eivät voi ainoastaan tyytyä tarkastelemaan kyseisellä menetelmällä saatuja tuloksia. Kuparipinnalle havaittiin, että korkeilla molekyylin kineettisen energian arvolla aikaisemmin suoritetut laskut hajottavista trajektoreista pitävät paikkansa, mutta matalilla kineettisen energian arvoilla molekyyli kohtaa erittäin voimakkaan ``steering'' vaikutuksen ja trajektorit joiden piti olla hajottavia johtavatkin molekulaariseen adsorptioon. Kun hapen konsentraatio pinnalla on suurempi kuin 0.5 ML, pinta rekonstruoituu. Myös rekonstruktion jälkeistä pintaa on tutkittu samanlaisilla menetelmillä kuin puhdasta pintaa. Rekonstruoituneelle pinnalle ei löydetty hajottavia trajektoreita ja havaittiin, että hapelle annetun kineettisen energian matalilla arvoilla myös tässä tapauksessa on erittäin voimakas ``steering'' vaikutus.

Hydrodynamics and Heat Transfer in an Airlift Reactor

Työn teoriaosassa esitetään kirjallisuudessa esiintyviä teoreettisia ja kokeellisia yhtälöitä nesteen nopeuden, kaasun tilavuusosuuden, painehäviön ja lämmönsiirron laskemiseksi. Lisäksi käsitellään airlift-reaktoreiden toimintaa, rakennetta ja teollisia sovelluksia, sekä sekoitusta ja geometrian vaikutusta airlift-reaktoreiden hydrodynaamisiin ominaisuuksiin. Kokeellisessa osassa kuvataan käytetty koelaitteisto ja mittausmenetelmät sekä esitetään saadut koetulokset. Koelaitteisto on viidellä nousuputkella varustettu ulkoisen kierron airlift-reaktori. Kokeellisessa osassa pyritään ratkaisemaan tällaisessa reaktorissa mahdollisesti esiintyviä ongelmia, kuten "slug flown" muodostuminen nousuputkissa sekä fluidien epätasainen jakautuminen nousuputkiin. Lisäksi tutkitaan erilaisten muuttujien, kuten kaasun tilavuusvirran, nesteen viskositeetin, suutinkoon ja nesteen jakoputken rakenteen, vaikutusta kaasun tilavuusosuuteen ja nesteen nopeuteen nousuputkissa. Nesteen nopeudet mitataan merkkiainemenetelmällä ja kaasun tilavuusosuudet manometrimenetelmällä. Lämmönsiirtoa tutkitaan mittaamalla lämpötilaeroja nousuputkissa NiCr-Ni –termoelementeillä. Mittaustulosten perusteella muokataan korrelaatiot kaasun tilavuusosuudelle ja nesteen tyhjäputkinopeudelle. Korrelaatioista lasketut tulokset sopivat kohtuullisen hyvin yhteen mitattujen tulosten kanssa. "Slug flown" ei todettu muodostuvan ongelmaksi 2.5 mPa s pienemmillä viskositeetin arvoilla 2 metriä pitkissä ja 19 mm halkaisijaltaan olevissa putkissa. Lisäksi todettiin, että kaasu- ja nestefaasien jakautumisongelmat voidaan ratkaista rakenteellisesti.

Combinative effects of β-Lapachone and APO866 on pancreatic cancer cell death through reactive oxygen species production and PARP-1 activation.

UNLABELLED: Pancreatic cancer (PC) is one of the most lethal human malignancies and a major health problem. Patients diagnosed with PC and treated with conventional approaches have an overall 5-year survival rate of less than 5%. Novel strategies are needed to treat this disease. Herein, we propose a combinatorial strategy that targets two unrelated metabolic enzymes overexpressed in PC cells: NAD(P)H: quinone oxidoreductase-1 (NQO1) and nicotinamide phosphoribosyl transferase (NAMPT) using β-lapachone (BL) and APO866, respectively. We show that BL tremendously enhances the antitumor activity of APO866 on various PC cell lines without affecting normal cells, in a PARP-1 dependent manner. The chemopotentiation of APO866 with BL was characterized by the following: (i) nicotinamide adenine dinucleotide (NAD) depletion; (ii) catalase (CAT) degradation; (iii) excessive H2O2 production; (iv) dramatic drop of mitochondrial membrane potential (MMP); and finally (v) autophagic-associated cell death. H2O2 production, loss of MMP and cell death (but not NAD depletion) were abrogated by exogenous supplementation with CAT or pharmacological or genetic inhibition of PARP-1. Our data demonstrates that the combination of a non-lethal dose of BL and low dose of APO866 optimizes significantly cell death on various PC lines over both compounds given separately and open new and promising combination in PC therapy.

Transfer pricing as a means for motivating management of profit centers

The main objective of this study is to analyze the role and potential of transfer pricing as a means of management control in large organizations. The special emphasis is on analyzing the potential of transfer pricing when we are motivating the profit center managers. The research approach is theoretical and literature reviews include studies about profit center organizations, performance measurement and analysis, incentive systems, transfer pricing techniques and agency theory. Based on the analysis, it seems that transfer pricing is a suitable tool for controlling, motivating and managing profit center managers. This requires that the performance measurement can be done fairly and transfer prices are set using fair assumptions. The motivating effects of transfer pricing can be enhanced if the reward system is connected to performance measurement system. In synthesis there is presented effects of transfer pricing to profit center managers behavior. There is also presented opinion about fair transfer pricing policy.