Browsing by Subject "AGGREGATION"

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  • Raerinne, Jani (2018)
    In addition to their core explanatory and predictive assumptions, scientific models include simplifying assumptions, which function as idealizations, approximations, and abstractions. There are methods to investigate whether simplifying assumptions bias the results of models, such as robustness analyses. However, the equally important issue - the focus of this paper - has received less attention, namely, what are the methodological and epistemic strengths and limitations associated with different simplifying assumptions. I concentrate on one type of simplifying assumption, the use of mega parameters as abstractions in ecological models. First, I argue that there are two kinds of mega parameters qua abstractions, sufficient parameters and aggregative parameters, which have gone unnoticed in the literature. The two are associated with different heuristics, holism and reductionism, which many view as incompatible. Second, I will provide a different analysis of abstractions and the associated heuristics than previous authors. Reductionism and holism and the accompanying abstractions have different methodological and epistemic functions, strengths, and limitations, and the heuristics should be viewed as providing complementary research perspectives of cognitively limited beings. This is then, third, used as a premise to argue for epistemic and methodological pluralism in theoretical ecology. Finally, the presented taxonomy of abstractions is used to comment on the current debate whether mechanistic accounts of explanation are compatible with the use of abstractions. This debate has suffered from an abstract discussion of abstractions. With a better taxonomy of abstractions the debate can be resolved.
  • Niemi, Tero; Kokkonen, Teemu; Sillanpää, Nora; Setälä, Heikki; Koivusalo, Harri (2019)
    Constructing hydrological models for large urban areas is time consuming and laborious due to the requirements for high-resolution data and fine model detail. An open-source algorithm using adaptive subcatchments is proposed to automate Storm Water Management Model (SWMM) construction. The algorithm merges areas with homogeneous land cover and a common outlet into larger subcatchments, while retaining small-scale details where land cover or topography is more heterogeneous. The method was tested on an 85-ha urban catchment in Helsinki, Finland. A model with adaptive subcatchments reproduced the observed discharge at the catchment outlet with high model-performance indices emphasizing the strength of the proposed method. Computation times of the adaptive model were substantially lower than those of a corresponding model with uniformly sized high-resolution subcatchments. Given that high-resolution land cover and topography data are available, the proposed algorithm provides an advanced method for implementing SWMM models automatically even for large urban catchments without a substantial manual workload. Simultaneously, the high-resolution land cover details of the catchments can be maintained where they matter the most. (c) 2019 American Society of Civil Engineers.
  • Kilpeläinen, Tommi; Julku, Ulrika; Svarcbahs, Reinis; Myöhänen, Timo (2019)
    Alpha-synuclein (aSyn) is the main component of Lewy bodies, the histopathological marker in Parkinson's disease (PD), and point mutations and multiplications of the aSyn coding SNCA gene correlate with early onset PD. Therefore, various transgenic mouse models overexpressing native or point-mutated aSyn have been developed. Although these models show highly increased aSyn expression they rarely capture dopaminergic cell loss and show a behavioural phenotype only at old age, whereas SNCA mutations are risk factors for PD with earlier onset. The aim of our study was to re-characterize a transgenic mouse strain carrying both A30P and A53T mutated human aSyn. Our study revealed decreased locomotor activity for homozygous transgenic mice starting from 3 months of age which was different from previous studies with this mouse strain that had behavioural deficits starting only after 7-9 months. Additionally, we found a decreased amphetamine response in locomotor activity and decreased extracellular dopaminergic markers in the striatum and substantia nigra with significantly elevated levels of aSyn oligomers. In conclusion, homozygous transgenic A30P*A53T aSyn mice capture several phenotypes of PD with early onset and could be a useful tool for aSyn studies.
  • Witos, Joanna; Karjalainen, Erno; Tenhu, Heikki; Wiedmer, Susanne K. (2020)
    Amphiphilic diblock copolymers consisting of a hydrophobic core containing a polymerized ionic liquid and an outer shell composed of poly(N-isoprolylacrylamide) were investigated by capillary electrophoresis and asymmetrical flow-field flow fractionation. The polymerized ionic liquid comprised poly(2-(1-butylimidazolium-3-yl)ethyl methacrylate tetrafluoroborate) with a constant block length (n = 24), while the length of the poly(N-isoprolylacrylamide) block varied (n = 14; 26; 59; 88). Possible adsorption of the block copolymer on the fused silica capillary, due to alterations in the polymeric conformation upon a change in the temperature (25 and 45 degrees C), was initially studied. For comparison, the effect of temperature on the copolymer conformation/hydrodynamic size was determined with the aid of asymmetrical flow-field flow fractionation and light scattering. To get more information about the hydrophilic/hydrophobic properties of the synthesized block copolymers, they were used as a pseudostationary phase in electrokinetic chromatography for the separation of some model compounds, that is, benzoates and steroids. Of particular interest was to find out whether a change in the length or concentration of the poly(N-isoprolylacrylamide) block would affect the separation of the model compounds. Overall, our results show that capillary electrophoresis and asymmetrical flow-field flow fractionation are suitable methods for characterizing conformational changes of such diblock copolymers.
  • Banić, Martina; Uroić, Ksenija; Leboš Pavunc, Andreja; Novak, Jasna; Zorić, Katarina; Durgo, Ksenija; Petković, Hrvoje; Jamnik, Polona; Kazazić, Saša; Kazazić, Snježana; Radović, Slobodanka; Scalabrin, Simone; Hynönen, Ulla; Šušković, Jagoda; Kos, Blaženka (2018)
    Abstract S-layers represent the simplest biological membranes developed during the evolution and are one of the most abundant biopolymers on Earth. Current fundamental and applied research aim to reveal the chemical structure, morphogenesis and function of S-layer proteins (Slps). This is the first paper that describes the Slps of certain Lactobacillus brevis strain isolated from sauerkraut. The whole genome sequence (WGS) analysis of the L. brevis SF9B strain uncovered three genes encoding the putative Slps, but merely one, identified as similar to the SlpB of L. brevis ATCC 14869, was expressed. Slp-expressing SF9B cells exhibited increased survival in simulated gastrointestinal (GI) conditions and during freeze-drying. Their survival in stress conditions was additionally enhanced by microencapsulation, especially when using alginate with gelatine as a matrix. Thus prepared cells were subjected to simulated GI conditions and their mortality was only 0.28 ± 0.45 log CFU/mL. Furthermore, a correlation between the high surface hydrophobicity and the remarkable aggregative capacity of SF9B strain was established. The results indicate a prominent role of Slps in adhesion to mucin, extracellular matrix (ECM) proteins, and particularly to Caco-2 cells, where the removal of Slps utterly abolished the adhesiveness of SF9B cells for 7.78 ± 0.25 log CFU/mL.
  • Ruokonen, Suvi-Katriina; Sanwald, Corinna; Robciuc, Alexandra; Hietala, Sami; Rantamäki, Antti H.; Witos, Joanna; King, Alistair W. T.; Lämmerhofer, Michael; Wiedmer, Susanne K. (2018)
    This study aims at extending the understanding of the toxicity mechanism of ionic liquids (ILs) using various analytical methods and cytotoxicity assays. The cytotoxicity of eight ILs and one zwitterionic compound was determined using mammalian and bacterial cells. The time dependency of the IL toxicity was assessed using human corneal epithelial cells. Hemolysis was performed using human red blood cells and the results were compared with destabilization data of synthetic liposomes upon addition of ILs. The effect of the ILs on the size and zeta potential of liposomes revealed information on changes in the lipid bilayer. Differential scanning calorimetry was used to study the penetration of the ILs into the lipid bilayer. Pulsed field gradient nuclear magnetic resonance spectroscopy was used to determine whether the ILs occurred as unimers, micelles, or if they were bound to liposomes. The results show that the investigated ILs can be divided into three groups based on the cytotoxicity mechanism: cell wall disrupting ILs, ILs exerting toxicity through both cell wall penetration and metabolic alteration, and ILs affecting solely on cell metabolism.
  • Vus, Kateryna; Girych, Mykhailo; Trusova, Valeriya; Gorbenko, Galyna; Kurutos, Atanas; Vasilev, Aleksey; Gadjev, Nikolai; Deligeorgiev, Todor (2019)
    The potential of novel cyanine dyes to inhibit the insulin amyloid formation was evaluated using thioflavin T fluorescence assay, quantum-chemical calculations, molecular docking and molecular dynamics simulations. According to the ability to suppress the insulin fibrillization under physiological conditions the examined compounds were found to follow the order: trimethines > pentamethines > monomethines > heptamethines. Of these, the trimethines 3-3 and 3-5, and pentamethines 5-3 and 5-9 almost completely prevented the protein aggregation by retarding both nucleation (except 3-3) and elongation processes. The quantum-chemical calculations revealed a complex relationship between the dye structure and its inhibitory effects. The molecular docking studies showed that most cyanines bind specifically to the L17 ladder of the B chain, located at the dry steric zipper of the insulin fibril protofilament, and form the stable complexes with the helices of the insulin monomer. The molecular dynamics simulations provided evidence for the increase of insulin helicity in the presence of cyanines. Collectively, the presented findings highlight two possible mechanisms by which cyanines can inhibit the insulin fibrillization: i) stabilization of the native protein structure followed by the retardation of the protein nucleation (all dyes); and ii) blocking the lateral extension of beta-sheets via the dye-protein stacking interactions (3-3, 3-5, 5-3, 5-9). Overall, the obtained results may prove of importance for the design of small molecules capable of preventing amyloid fibril formation by insulin and other proteins. (C) 2018 Elsevier B.V. All rights reserved.
  • Laine, Outi; Joutsi-Korhonen, Lotta; Lassila, Riitta; Huhtala, Heini; Vaheri, Antti; Makela, Satu; Mustonen, Jukka (2016)
    We evaluated the mechanisms of thrombocytopenia and procoagulant changes in relation with clinical variables in a cohort of patients with acute hantavirus disease. Blood samples of 33 prospectively recruited, consecutive, hospitalized patients with acute Puumala virus-induced hemorrhagic fever with renal syndrome (HFRS) were collected acutely and at the recovery visit (control). Serum thrombopoietin (TPO) and activity of plasma microparticles (MPs) from various cell sources were measured with enzyme-linked immunosorbent assay-based methods. The results were related to data on platelet indices and functions, coagulation variables, and clinical disease. Serum TPO was nearly 4-fold higher acutely compared with the control (median 207pg/mL, range 56-1258pg/mL vs. median 58 pg/mL, range 11-241pg/mL, P Upregulated TPO together with high MPV and IPF% confirm active thrombopoiesis, but do not predict severity of HFRS. Simultaneously, elevated prothrombin fragments and D-dimer suggest increased consumption of platelets in patients with severe AKI. Activity of platelet-derived MPs in HFRS should be studied with flow cytometry in a larger cohort of patients.
  • Nissila, Eija; Douillard, Francois P.; Ritari, Jarmo; Paulin, Lars; Jarvinen, Hanna M.; Rasinkangas, Pia; Haapasalo, Karita; Meri, Seppo; Jarva, Hanna; de Vos, Willem M. (2017)
    Lactobacillus rhamnosus strains are ubiquitous in fermented foods, and in the human body where they are commensals naturally present in the normal microbiota composition of gut, vagina and skin. However, in some cases, Lactobacillus spp. have been implicated in bacteremia. The aim of the study was to examine the genomic and immunological properties of 16 clinical blood isolates of L. rhamnosus and to compare them to the well- studied L. rhamnosus probiotic strain GG. Blood cultures from bacteremic patients were collected at the Helsinki University Hospital laboratory in 2005-2011 and L. rhamnosus strains were isolated and characterized by genomic sequencing. The capacity of the L. rhamnosus strains to activate serum complement was studied using immunological assays for complement factor C3a and the terminal pathway complement complex (TCC). Binding of complement regulators factor H and C4bp was also determined using radioligand assays. Furthermore, the isolated strains were evaluated for their ability to aggregate platelets and to form biofilms in vitro. Genomic comparison between the clinical L. rhamnosus strains showed them to be clearly different from L. rhamnosus GG and to cluster in two distinct lineages. All L. rhamnosus strains activated complement in serum and none of them bound complement regulators. Four out of 16 clinical blood isolates induced platelet aggregation and/or formed more biofilms than L. rhamnosus GG, which did not display platelet aggregation activity nor showed strong biofilm formation. These findings suggest that clinical L. rhamnosus isolates show considerable heterogeneity but are clearly different from L. rhamnosus GG at the genomic level. All L. rhamnosus strains are still normally recognized by the human complement system.
  • Reckling, Moritz; Döring, Thomas F.; Bergkvist, Göran; Stoddard, Frederick L.; Watson, Christine A.; Seddig, Sylvia; Chmielewski, Frank-M.; Bachinger, Johann (2018)
    Grain legumes produce high-quality protein for food and feed, and potentially contribute to sustainable cropping systems, but they are grown on only 1.5% of European arable land. Low temporal yield stability is one of the reasons held responsible for the low proportion of grain legumes, without sufficient quantitative evidence. The objective of this study was to compare the yield stability of grain legumes with other crop species in a northern European context and accounting for the effects of scale in the analysis and the data. To avoid aggregation biases in the yield data, we used data from long-term field experiments. The experiments included grain legumes (lupin, field pea, and faba bean), other broad-leaved crops, spring, and winter cereals. Experiments were conducted in the UK, Sweden, and Germany. To compare yield stability between grain legumes and other crops, we used a scale-adjusted yield stability indicator that accounts for the yield differences between crops following Taylor's Power Law. Here, we show that temporal yield instability of grain legumes (30%) was higher than that of autumn-sown cereals (19%), but lower than that of other spring-sown broad-leaved crops (35%), and only slightly greater than spring-sown cereals (27%). With the scale-adjusted yield stability indicator, we estimated 21% higher yield stability for grain legumes compared to a standard stability measure. These novel findings demonstrate that grain legume yields are as reliable as those of other spring-sown crops in major production systems of northern Europe, which could influence the current negative perception on grain legume cultivation. Initiatives are still needed to improve the crops agronomy to provide higher and more stable yields in future.
  • Moiseev, Dmitry; Lautaportti, Susanna; Alku, Laura; Tabakova, Ksenia; O'Connor, Ewan; Leskinen, Matti; Kulmala, Markku (2019)
    Abstract: Eleven years of dual-polarization weather radar data, complemented by satellite and lidar observations, were used to investigate the origin of areas of localized intensification of precipitation spotted in the vicinity of Helsinki-Vantaa airport. It was observed that existing precipitation is enhanced locally on spatial scales from a few kilometers to several tens of kilometers. The precipitation intensity in these localized areas was 6-14 times higher than the background large-scale precipitation rate. Surface observations and dual-polarization radar data indicate that snowflakes within the ice portion of the falling precipitation in the intensification regions are larger and more isotropic than in the surrounding precipitation. There appears to be an increase in the ice particle number concentration within the intensification region. The observed events were linked to arriving or departing air traffic. We advocate that the mechanism responsible for intensification is aircraft-produced ice particles boosting the aggregation growth of snowflakes. Plain Language Summary: By analyzing 11 years of dual-polarization weather radar observations in the Helsinki region, we have discovered that airplanes landing in or departing from the Helsinki-Vantaa airport could locally increase precipitation rate by as much as 14 times. The observed phenomenon is related to the hole-punch clouds, which are also forming with the help of airplanes. The reported observations allow us to have a better understanding of precipitation formation processes that take place in ice and mixed phase clouds. They show that falling ice crystals from upper clouds could seed lower clouds and therefore increase rain or snowfall intensity through the process called snowflake aggregation. During snowflake aggregation bigger faster falling particles are formed by ice particles colliding and sticking together.
  • Kneifel, Stefan; Moisseev, Dmitri (2020)
    Riming is an efficient process of converting liquid cloud water into ice and plays an important role in the formation of precipitation in cold clouds. Due to the rapid increase in ice particle mass, riming enhances the particle's terminal velocity, which can be detected by ground-based vertically pointing cloud radars if the effect of vertical air motions can be sufficiently mitigated. In our study, we first revisit a previously published approach to relate the radar mean Doppler velocity (MDV) to rime mass fraction (FR) using a large ground-based in situ dataset. This relation is then applied to multiyear datasets of cloud radar observations collected at four European sites covering polluted central European, clean maritime, and Arctic climatic conditions. We find that riming occurs in 1%-8% of the nonconvective ice containing clouds with median FR between 0.5 and 0.6. Both the frequency of riming and FR reveal relatively small variations for different seasons. In contrast to previous studies, which suggested enhanced riming for clean environments, our statistics indicate the opposite; however, the differences between the locations are overall small. We find a very strong relation between the frequency of riming and temperature. While riming is rare at temperatures lower than -12 degrees C, it strongly increases toward 0 degrees C. Previous studies found a very similar temperature dependence for the amount and droplet size of supercooled liquid water, which might be closely connected to the riming signature found in this study. In contrast to riming frequency, we find almost no temperature dependence for FR.
  • Palmio, Johanna; Jonson, Per Harald; Inoue, Michio; Sarparanta, Jaakko; Bengoechea, Rocio; Savarese, Marco; Vihola, Anna; Jokela, Manu; Nakagawa, Masanori; Noguchi, Satoru; Olivé, Montse; Masingue, Marion; Kerty, Emilia; Hackman, Peter; Weihl, Conrad C.; Nishino, Ichizo; Udd, Bjarne (2020)
    Eight patients from five families with undiagnosed dominant distal myopathy underwent clinical, neurophysiological and muscle biopsy examinations. Molecular genetic studies were performed using targeted sequencing of all known myopathy genes followed by segregation of the identified mutations in the affected families using Sanger sequencing. Two novel mutations in DNAJB6 J domain, c.149C>T (p.A50V) and c.161A>C (p.E54A), were identified as the cause of disease. The muscle involvement with p.A50V was distal calf-predominant, and the p.E54A was more proximo-distal. Histological findings were similar to those previously reported in DNAJB6 myopathy. In line with reported pathogenic mutations in the glycine/phenylalanine (G/F) domain of DNAJB6, both the novel mutations showed reduced anti-aggregation capacity by filter trap assay and TDP-43 disaggregation assays. Modeling of the protein showed close proximity of the mutated residues with the G/F domain. Myopathy-causing mutations in DNAJB6 are not only located in the G/F domain, but also in the J domain. The identified mutations in the J domain cause dominant distal and proximo-distal myopathy, confirming that mutations in DNAJB6 should be considered in distal myopathy cases.
  • Myöhänen, Timo T.; Norrbacka, Susanna; Savolainen, Mari H. (2017)
    Lewy bodies, the histopathological hallmarks of Parkinson's disease (PD), contain insoluble and aggregated alpha-synuclein (aSyn) and many other proteins, proposing a role for failure in protein degradation system in the PD pathogenesis. Proteasomal dysfunction has indeed been linked to PD and aSyn oligomers have been shown to inhibit proteasomes and autophagy. Our recent studies have shown that inhibitors of prolyl oligopeptidase (PREP) can prevent the aggregation and enhance the clearance of accumulated aSyn, and therefore, we wanted to study if PREP inhibition can overcome the aSyn aggregation and toxicity induced by lactacystin, a proteasomal inhibitor. The cells overexpressing human A30P or A53T mutated aSyn were incubated with lactacystin and a PREP inhibitor, KYP-2047, for 48 h. Theafter, the cells were fractioned, and the effects of lactacystin with/without 1 mu M KYP-2047 on aSyn aggregation and ubiquitin accumulation, cell viability and on autophagic markers (p62, Beclin1 and LC3BII) were studied. We found that KYP-2047 attenuated lactacystin-induced cell death in mutant aSyn overexpressing cells but not in non-overexpressing control cells. KYP-2047 reduced significantly SDS-insoluble high-molecular-weight aSyn oligomers that were in line with the cell viability results. In addition, significant reduction in protein accumulation marker, p62, was seen in SDS fraction while LC3BII, a marker for autophagosome formation, was increased, indicating to enhanced autophagy. Our results further streghten the possibilities for PREP inhibitors as a potential drug therapy against synucleinopathies and other protein aggregating diseases. (C) 2016 Elsevier Ireland Ltd. All rights reserved.
  • Eteläinen, T.; Kulmala, Soile; Svarcbahs, R.; Jäntti, M.; Myohänen, T. T. (2021)
    Oxidative stress (OS) is a common toxic feature in various neurodegenerative diseases. Therefore, reducing OS could provide a potential approach to achieve neuroprotection. Prolyl oligopeptidase (PREP) is a serine protease that is linked to neurodegeneration, as endogenous PREP inhibits autophagy and induces the accumulation of detrimental protein aggregates. As such, inhibition of PREP by a small-molecular inhibitor has provided neuroprotection in preclinical models of neurodegenerative diseases. In addition, PREP inhibition has been shown to reduce production of reactive oxygen species (ROS) and the absence of PREP blocks stress-induced ROS production. However, the mechanism behind PREP-related ROS regulation is not known. As we recently discovered PREP's physiological role as a protein phosphatase 2A (PP2A) regulator, we wanted to characterize PREP inhibition as an approach to reduce OS. We studied the impact of a PREP inhibitor, KYP-2047, on hydrogen peroxide and ferrous chloride induced ROS production and on cellular antioxidant response in HEK-293 and SHSY5Y cells. In addition, we used HEK-293 and SH-SY5Y PREP knock-out cells to validate the role of PREP on stress-induced ROS production. We were able to show that absence of PREP almost entirely blocks the stressinduced ROS production in both cell lines. Reduced ROS production and smaller antioxidant response was also seen in both cell lines after PREP inhibition by 10 mu M KYP-2047. Our results also revealed that the OS reducing mechanism of PREP inhibition is related to reduced activation of ROS producing NADPH oxidase through enhanced PP2A activation. In conclusion, our results suggest that PREP inhibition could also provide neuroprotection by reducing OS, thus broadening the scope of its beneficial effects on neurodegeneration.
  • Steffen, Hannah L. M.; Anderson, Josephine L. C.; Poot, Margot L.; Lei, Yu; Connelly, Margery A.; Bakker, Stephan J. L.; Öörni, Katariina; Tietge, Uwe J. F. (2021)
    Lipoprotein-proteoglycan binding is an early key event in atherosclerotic lesion formation and thus conceivably could play a major role in vasculopathy-driven chronic graft failure and cardiovascular mortality in renal transplant recipients. The present study investigated whether lipoproteinproteoglycan binding susceptibility (LPBS) of apoBcontaining lipoproteins and levels of the classical atherosclerosis biomarker LDL-C were associated with cardiovascular mortality (n = 130) and graft failure (n = 73) in 589 renal transplant recipients who were followed up from at least 1 year after transplantation for 9.5 years. At baseline, LPBS was significantly higher in patients who subsequently developed graft failure than in those with a surviving graft (1.68 +/- 0.93 vs. 1.46 +/- 0.49 nmol/mmol, P = 0.001). Cox regression analysis showed an association between LPBS and chronic graft failure in an age-and sex-adjusted model (hazard ratio: 1.45; 95% CI, 1.14-1.85; P = 0.002), but no association was observed with cardiovascular mortality. LDL-C levels were not associated with graft failure or cardiovascular mortality. This study shows that measurement of cholesterol retention outperformed the traditionally used quantitative parameter of LDL-C levels in predicting graft failure, suggesting a higher relevance of proatherogenic function than the quantity of apoBcontaining lipoproteins in chronic kidney graft failure.
  • Merezhko, Maria; Brunello, Cecilia A.; Yan, Xu; Vihinen, Helena; Jokitalo, Eija; Uronen, Riikka-Liisa; Huttunen, Henri J. (2018)
    Tauopathies are characterized by cerebral accumulation of Tau protein aggregates that appear to spread throughout the brain via a cell-to-cell transmission process that includes secretion and uptake of pathological Tau, followed by templated misfolding of normal Tau in recipient cells. Here, we show that phosphorylated, oligomeric Tau clusters at the plasma membrane in N2A cells and is secreted in vesicle-free form in an unconventional process sensitive to changes in membrane properties, particularly cholesterol and sphingomyelin content. Cell surface heparan sulfate proteoglycans support Tau secretion, possibly by facilitating its release after membrane penetration. Notably, secretion of endogenous Tau from primary cortical neurons is mediated, at least partially, by a similar mechanism. We suggest that Tau is released from cells by an unconventional secretory mechanism that involves its phosphorylation and oligomerization and that membrane interaction may help Tau to acquire properties that allow its escape from cells directly through the plasma membrane.
  • Hassan, Alaa A.; Mohamed, Nasr K.; Aly, Ashraf A.; Tawfeek, Hendawy N.; Bräse, Stefan; Nieger, Martin (2019)
    In this investigation the synthesis of diazenylthiazoles (3a-e) by the reaction of arylthiosemicarbazides with omega-bromoacetophenones via Eschenmoser-coupling reaction in acetonitrile and equimolar amounts of triethylamine and triphenylphosphine. Upon heating 1,4-disubstituted thiosemicarbazides with omega-bromoacetophenones in absolute ethanol, hydrazothiazoles (16a-i) were precipitated. On the other hand, the reaction of arylthiosemicarbazides with omega-bromoacetophenones in refluxing ethanol yielded 2-amino-5-[4-aminophenyl]-4-phenylthiazolium bromide dihydrate derivatives (19a-g) via [5.5] sigmatropic shift. The studied products were further characterized by IR, H-1 NMR, C-13 NMR and mass spectrometry. X-ray single crystal of 3a and 16h showed that, the molecules crystallized in the triclinic crystal system, space group P2(1)/c. Whereas the X-ray single crystal of 19b showed the molecule crystalized in orthorhombic, space group P2(1)2(1)2(1). In the crystal of 19b, the lattice water and bromide ion associated through hydrogen bonded with thiazole-NH2. (C) 2018 Published by Elsevier B.V.
  • Mason, Shannon L.; Hogan, Robin J.; Westbrook, Christopher D.; Kneifel, Stefan; Moisseev, Dmitri; von Terzi, Leonie (2019)
    The accurate representation of ice particles is essential for both remotely sensed estimates of clouds and precipitation and numerical models of the atmosphere. As it is typical in radar retrievals to assume that all snow is composed of aggregate snowflakes, both denser rimed snow and the mixed-phase cloud in which riming occurs may be under-diagnosed in retrievals and therefore difficult to evaluate in weather and climate models. Recent experimental and numerical studies have yielded methods for using triple-frequency radar measurements to interrogate the internal structure of aggregate snowflakes and to distinguish more dense and homogeneous rimed particles from aggregates. In this study we investigate which parameters of the morphology and size distribution of ice particles most affect the triple-frequency radar signature and must therefore be accounted for in order to carry out triple-frequency radar retrievals of snow. A range of ice particle morphologies are represented, using a fractal representation for the internal structure of aggregate snowflakes and homogeneous spheroids to represent graupel-like particles; the mass-size and area-size relations are modulated by a density factor. We find that the particle size distribution (PSD) shape parameter and the parameters controlling the internal structure of aggregate snowflakes both have significant influences on triple-frequency radar signature and are at least as important as that of the density factor. We explore how these parameters may be allowed to vary in order to prevent triple-frequency radar retrievals of snow from being over-constrained, using two case studies from the Biogenic Aerosols - Effects of Clouds and Climate (BAECC) 2014 field campaign at Hyytiala, Finland. In a case including heavily rimed snow followed by large aggregate snowflakes, we show that triple-frequency radar measurements provide a strong constraint on the PSD shape parameter, which can be estimated from an ensemble of retrievals; however, resolving variations in the PSD shape parameter has a limited impact on estimates of snowfall rate from radar. Particle density is more effectively constrained by the Doppler velocity than triple-frequency radar measurements, due to the strong dependence of particle fall speed on density. Due to the characteristic signatures of aggregate snowflakes, a third radar frequency is essential for effectively constraining the size of large aggregates. In a case featuring rime splintering, differences in the internal structures of aggregate snowflakes are revealed in the triple-frequency radar measurements. We compare retrievals assuming different aggregate snowflake models against in situ measurements at the surface and show significant uncertainties in radar retrievals of snow rate due to changes in the internal structure of aggregates. The importance of the PSD shape parameter and snowflake internal structure to triple-frequency radar retrievals of snow highlights that the processes by which ice particles interact may need to be better understood and parameterized before triple-frequency radar measurements can be used to constrain retrievals of ice particle morphology.
  • Gasecka, Aleksandra; Nieuwland, Rienk; Budnik, Monika; Dignat-George, Francoise; Eyileten, Ceren; Harrison, Paul; Lacroix, Romaric; Leroyer, Aurelie; Opolski, Grzegorz; Pluta, Kinga; van der Pol, Edwin; Postula, Marek; Siljander, Pia; Siller-Matula, Jolanta M.; Filipiak, Krzysztof J. (2020)
    Background Platelet P2Y12 antagonist ticagrelor reduces mortality after acute myocardial infarction (AMI) compared to clopidogrel, but the underlying mechanism is unknown. Because activated platelets, leukocytes, and endothelial cells release proinflammatory and prothrombotic extracellular vesicles (EVs), we hypothesized that the release of EVs is more efficiently inhibited by ticagrelor compared to clopidogrel. Objectives We compared EV concentrations and EV procoagulant activity in plasma of patients after AMI treated with ticagrelor or clopidogrel. Methods After percutaneous coronary intervention, 60 patients with first AMI were randomized to ticagrelor or clopidogrel. Flow cytometry was used to determine concentrations of EVs from activated platelets (CD61(+), CD62p(+)), fibrinogen(+), phosphatidylserine (PS+), leukocytes (CD45(+)), endothelial cells (CD31(+), 146(+)), and erythrocytes (CD235a(+)) in plasma at randomization, after 72 hours and 6 months of treatment. A fibrin generation test was used to determine EV procoagulant activity. Results Concentrations of platelet, fibrinogen(+), PS+, leukocyte, and erythrocyte EVs increased 6 months after AMI compared to the acute phase of AMI (P = .17). Conclusions Ticagrelor attenuates the increase of EV concentrations in plasma after acute myocardial infarction compared to clopidogrel. The ongoing release of EVs despite antiplatelet therapy might explain recurrent thrombotic events after AMI and worse clinical outcomes on clopidogrel compared to ticagrelor.