Browsing by Subject "FORMS"

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  • Gorbikova, Elena; Kalendar, Ruslan (2020)
    Cytochrome c oxidase is terminal enzyme in the respiratory chain of mitochondria and many aerobic bacteria. It catalyzes reduction of oxygen to water. During its catalysis, CcO proceeds through several quite stable intermediates (R, A, PR/M, O/OH, E/EH). This work is concentrated on the elucidation of the differences between structures of oxidized intermediates O and OH in different CcO variants and at different pH values. Oxidized intermediates of wild type and mutated CcO from Paracoccus denitrificans were studied by means of static and time-resolved Fourier-transform infrared spectroscopy in acidic and alkaline conditions in the infrared region 1800–1000 cm−1. No reasonable differences were found between all variants in these conditions, and in this spectral region. This finding means that the binuclear center of oxygen reduction keeps a very similar structure and holds the same ligands in the studied conditions. The further investigation in search of differences should be performed in the 4000–2000 cm−1 IR region where water ligands absorb.
  • Palomäki, Emmi A. K.; Yliruusi, Jouko K.; Ehlers, Henrik (2019)
    In this paper, the effect of the gaseous environment on recrystallization of amorphous paracetamol was investigated. The experiments were conducted with a headspace gas consisting of dry air, dry carbon dioxide, dry nitrogen and humid air in four temperatures ranging from 5 degrees C below onset of T-g to 5 degrees C above onset of T-g. The recrystallization was monitored using Raman spectroscopy and subsequent multivariate analysis. In temperatures below onset of T-g, the presence of oxygen delayed the onset of recrystallization, with an increasing delay with lower temperature. When comparing samples exposed to dry headspace gases, the crystallization was fastest below onset of Tg when exposed to nitrogen. Being an inert gas, nitrogen did not seem to interfere with the molecules allowing them to freely find their inherent arrangement, whereas the presence of oxygen delayed the formation of stabile nuclei. Above onset of T-g, no differences in onset of crystallization was detected between dry gas atmospheres. Amorphous paracetamol crystallized to form II in all measurements and the samples did not reach full crystallinity within the duration of the experiments. The results show that the headspace gas has an effect on nucleation in the amorphous sample.
  • Bonora, L.; Bytsenko, A. A.; Chaichian, M. (2015)
    We analyze the characteristic series, the KO series and the series associated with the Witten genus, and their analytic forms as the q-analogs of classical special functions (in particular q-analog of the beta integral and the gamma function). q-Series admit an analytic interpretation in terms of the spectral Ruelle functions, and their relations with appropriate elliptic modular forms can be described. We show that there is a deep correspondence between the characteristic series of the Witten genus and KO characteristic series, on one side, and the denominator identities and characters of N = 2 superconformal algebras, and the affine Lie (super)algebras on the other. We represent the characteristic series in the form of double series using the Hecke-Rogers modular identity. (C) 2015 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY license.
  • Anwar, Tahira; Liu, Xiaonan; Suntio, Taina; Marjamäki, Annika; Biazik, Joanna; Chan, Edmond Y. W.; Varjosalo, Markku; Eskelinen, Eeva-Liisa (2019)
    Autophagy transports cytoplasmic material and organelles to lysosomes for degradation and recycling. Beclin 1 forms a complex with several other autophagy proteins and functions in the initiation phase of autophagy, but the exact role of Beclin 1 subcellular localization in autophagy initiation is still unclear. In order to elucidate the role of Beclin 1 localization in autophagosome biogenesis, we generated constructs that target Beclin 1 to the endoplasmic reticulum (ER) or mitochondria. Our results confirmed the proper organelle-specific targeting of the engineered Beclin 1 constructs, and the proper formation of autophagy-regulatory Beclin 1 complexes. The ULK kinases are required for autophagy initiation upstream of Beclin 1, and autophagosome biogenesis is severely impaired in ULK1/ULK2 double knockout cells. We tested whether Beclin 1 targeting facilitated its ability to rescue autophagosome formation in ULK1/ULK2 double knockout cells. ER-targeted Beclin 1 was most effective in the rescue experiments, while mitochondria-targeted and non-targeted Beclin 1 also showed an ability to rescue, but with lower activity. However, none of the constructs was able to increase autophagic flux in the knockout cells. We also showed that wild type Beclin 1 was enriched on the ER during autophagy induction, and that ULK1/ULK2 facilitated the ER-enrichment of Beclin 1 under basal conditions. The results suggest that one of the functions of ULK kinases may be to enhance Beclin 1 recruitment to the ER to drive autophagosome formation.
  • Hokkala, Emma; Strachan, Clare J.; Agopov, Mikael; Semjonov, Kristian; Heinämäki, Jyrki; Yliruusi, Jouko; Svanback, Sami (2022)
    The solubility and dissolution rates of chemical compounds are crucial properties in several fields of industry and research. However, accurate, rapid and green methods for their measurement, which only consume micrograms of compound, are lacking. Here, the unique approach of non-specific, image-based single particle analysis (SPA) for solubility testing is directly compared to and thus validated on the mid-solubility range with the current gold standard shake-flask method with UV-Vis spectroscopy employed for determining sample concentrations. Five biologically active compounds representing a range of physicochemical properties including pK(a) and logP were analyzed with both methods. The comparison of SPA and the shake-flask (SF) analysis shows excellent linear correlation (R-2 = 0.99). Higher variability of the SPA method is attributed to variability between the properties of individual particles, which cannot be detected with traditional methods. Due to the similar average solubility values compared to those produced with SF, it is concluded that the SPA method has great potential as an analytical tool for small-scale solubility studies. It also has several practical advantages over the current gold standard shake-flask method, such as speed, low consumables consumption, and no requirement for prior knowledge of compound chemistry.
  • Boss, Marti; Rottenburger, Christof; Brenner, Winfried; Blankenstein, Oliver; Prasad, Vikas; Prasad, Sonal; de Coppi, Paolo; Kuhnen, Peter; Buitinga, Mijke; Nuutila, Pirjo; Otonkoski, Timo; Hussain, Khalid; Brom, Maarten; Eek, Annemarie; Bomanji, Jamshed; Shah, Pratik; Gotthardt, Martin (2022)
    Surgery with curative intent can be offered to congenital hyperinsulinism (CHI) patients, provided that the lesion is focal. Radiolabeled exendin-4 specifically binds the glucagonlike peptide 1 receptor on pancreatic beta-cells. In this study, we compared the performance of F-18-DOPA PET/CT, the current standard imaging method for CHI, and PET/CT with the new tracer Ga-68-NODAGA-exendin-4 in the preoperative detection of focal CHI. Methods: Nineteen CHI patients underwent both F-18-DOPA PET/CT and Ga-68-NODAGA-exendin-4 PET/CT before surgery. The images were evaluated in 3 settings: a standard clinical reading, a masked expert reading, and a joint reading. The target (lesion)-to-nontarget (normal pancreas) ratio was determined using SUVmax. Image quality was rated by pediatric surgeons in a questionnaire. Results: Fourteen of 19 patients having focal lesions underwent surgery. On the basis of clinical readings, the sensitivity of Ga-68-NODAGA-exendin-4 PET/CT (100%; 95% CI, 77%-100%) was higher than that of F-18-DOPA PET/CT (71%; 95% CI, 42%-92%). Interobserver agreement between readings was higher for Ga-68-NODAGA-exendin-4 than for F-18-DOPA PET/CT (Fleiss kappa = 0.91 vs. 0.56). Ga-68-NODAGA-exendin-4 PET/CT provided significantly (P = 0.021) higher target-to-nontarget ratios (2.02 +/- 0.65) than did F-18-DOPA PET/CT (1.40 +/- 0.40). On a 5-point scale, pediatric surgeons rated Ga-68-NODAGA-exendin-4 PET/CT as superior to F-18-DOPA PET/CT. Conclusion: For the detection of focal CHI, Ga-68-NODAGA-exendin-4 PET/CT has higher clinical sensitivity and better interobserver correlation than F-18-DOPA PET/CT. Better contrast and image quality make Ga-68-NODAGA-exendin-4 PET/CT superior to F-18-DOPA PET/CT in surgeons' intraoperative quest for lesion localization.
  • Robciuc, Marius R.; Metso, Jari; Sima, Anca; Ehnholm, Christian; Jauhiainen, Matti (2010)
    Background: phospholipid transfer protein (PLTP) plays important roles in lipoprotein metabolism and atherosclerosis and is expressed by macrophages and macrophage foam cells (MFCs). The aim of the present study was to determine whether the major protein from HDL, apoA-I, affects PLTP derived from MFCs. Results: as cell model we used human THP-1 monocytes incubated with acetylated LDL, to generate MFC. The addition of apoA-I to the cell media increased apoE secretion from the cells, in a concentration dependent fashion, without affecting cellular apoE levels. In contrast, apoA-I had no effect on PLTP synthesis and secretion, but strongly induced the PLTP activity in the media. ApoA-I also increased phospholipid transfer activity of PLTP isolated from human plasma. This effect was dependent on apoA-I concentration but independent on apoA-I lipidation status. ApoE, ApoA-II and apoA-IV, but not immunoglobulins or bovine serum albumin, also increased PLTP activity. We also report that apoA-I protects PLTP from heat inactivation. Conclusion: apoA-I enhances the phospholipid transfer activity of PLTP secreted from macrophage foam cells without affecting the PLTP mass.
  • Stukelj, Jernej; Agopov, Mikael; Yliruusi, Jouko; Strachan, Clare J.; Svanbäck, Sami (2020)
    Poor solubility of crystalline drugs can be overcome by amorphization - the production of high-energy disordered solid with improved solubility. However, the improved solubility comes at a cost of reduced stability; amorphous drugs are prone to recrystallization. Because of recrystallization, the initial solubility enhancement is eventually lost. Therefore, it is important to understand the recrystallization process during storage of amorphous materials and its impact on dissolution/solubility. Here, we demonstrate the use of image-based single-particle analysis (SPA) to consistently monitor the solubility of an amorphous indomethacin sample over time. The results are compared to the XRPD signal of the same sample. For the sample stored at 22 degrees C/23 % relative humidity (RH), full crystallinity as indicated by XRPD was reached around day 40, whereas a solubility corresponding to that of the. crystalline form was measured with SPA at day 25. For the sample stored at 22 degrees C/75 % RH, the XRPD signal indicated a rapid initial phase of crystallization. However, the sample failed to fully crystallize in 80 days. With SPA, solubility slightly above that of the crystalline. form was measured already on the second day. To conclude, the solubility measured with SPA directly reflects the solid-state changes occurring on the particle surface. Therefore, it can provide vital information - in a straightforward manner while requiring only minuscule sample amounts - for understanding the effect of storage conditions on the dissolution/solubility of amorphous materials, especially important in pharmaceutical science.
  • Liebkind, Karmela; Mäkinen, Viivi M; Jasinskaja-Lahti, Inga; Renvik (Mähönen), Tuuli Anna; Solheim, Erling (2019)
    Despite the urgent need for promoting positive intergroup relations in schools, research on intergroup relations is not systematically translated into prejudice-reduction interventions. Although prejudice-reduction interventions in schools based on indirect contact have been conducted for decades, they have all been carried out by researchers themselves. In a field experiment in Finland in autumn 2015, we tested for the first time a vicarious contact prejudice-reduction intervention for its effectiveness among adolescents (N = 639) when implemented independently by school teachers instead of researchers. In addition, we tested the extent to which the intervention’s effect depends on initial outgroup attitudes, previous direct outgroup contact experiences, and gender, hypothesizing that the intervention improves outgroup attitudes particularly among adolescents with more negative prior attitudes and less positive prior direct contact, and more among girls than among boys. We found an unanticipated overall deterioration in the outgroup attitudes during intervention in both the experimental and control groups. However, attitudes seemed to deteriorate somewhat less in the experimental than in the control group, and the intervention had a significant positive effect on outgroup attitudes in one experimental subgroup that needed it most: girls who had negative rather than positive outgroup attitudes at the outset. We discuss our results in light of previous research and contextual particularities.
  • Kiani, Mina; Tammeorg, Priit; Niemistö, Juha; Simojoki, Asko; Tammeorg, Olga (2020)
    Mankind is taking advantage of numerous services by small shallow lakes such as drinking water supply, irrigation, and recreational function; however, many of these lakes suffer from eutrophication. Given the key role of phosphorus (P) in eutrophication process, one of the effective restoration methods especially for small shallow lakes is removal of sediments enriched with nutrients. In our study, we used interannual, seasonal, and spatial data to examine the changes in sediment P mobility after removal of sediments in 2016 from a 1-ha highly eutrophic lake. We measured the sediment redox potential, analyzed soluble reactive P (SRP) in the pore water and P fractional composition of the surface sediments, and calculated the P diffusive flux in three locations in two continuous years (2017 and 2018) after the excavation. Similar measurements were done before sediment removal at central site of the lake in 2015. Removing nutrient-rich sediment also removed 6400 kg of P, and thus the potential for release of P from sediments decreased on a long-term scale. However, a large pool of releasable P was rebuilt soon after the sediment removal due to high external P loading, resulting in extensive anoxia of sediment surface and associated internal P loading as high as 1450 mg m−2 summer−1. Moreover, the Fe-P and labile P fractions were the most important sources of P release, as evidenced by their considerable seasonal and interannual changes after the sediment removal. The sediment total Fe negatively correlated with sediment P diffusive flux, pore water SRP, and near-bottom water total P and SRP concentrations which indicated a strong linkage between sediment P dynamics and Fe after the restoration. Sediment removal could be a beneficial restoration approach, but the effects on lake water quality remain only short-term unless there is an adequate control on external loading to the lake.
  • Fox, Barbara A.; Heinemann, Trine (2017)
    In previous interactional studies of formats for utterances doing requests, attention has been given to the initial verb (such as can/could or wonder) and possibly the subject (especially I vs you). The current study examines the main types of grammatical variation found in what we call the " x component," that is the segment after the initial verb and subject. We examine two types of requests: those with can you x and those with wonder x, and we find that variations in the x component in these requests are associated with variations in the unfolding development of the request sequences. We thus suggest that the x component is crucial to the interactional work accomplished by the requesting utterance.
  • Augustine, Erika F.; Adams, Heather R.; de los Reyes, Emily; Drago, Kristen; Frazier, Margie; Guelbert, Norberto; Laine, Minna; Levin, Tanya; Mink, Jonathan W.; Nickel, Miriam; Peifer, Danielle; Schulz, Angela; Simonati, Alessandro; Topcu, Meral; Turunen, Joni A.; Williams, Ruth; Wirrell, Elaine C.; King, Sharon (2021)
    Background: CLN1 disease (neuronal ceroid lipofuscinosis type 1) is a rare, genetic, neurodegenerative lysosomal storage disorder caused by palmitoyl-protein thioesterase 1 (PPT1) enzyme deficiency. Clinical features include developmental delay, psychomotor regression, seizures, ataxia, movement disorders, visual impairment, and early death. In general, the later the age at symptom onset, the more protracted & nbsp;Pediatric Neurology 120 (2021) 38e51 the disease course. We sought to evaluate current evidence and to develop expert practice consensus to support clinicians who have not previously encountered patients with this rare disease. Methods: We searched the literature for guidelines and evidence to support clinical practice recommendations. We surveyed CLN1 disease experts and caregivers regarding their experiences and recommendations, and a meeting of experts was conducted to ascertain points of consensus and clinical practice differences. Results: We found a limited evidence base for treatment and no clinical management guidelines specific to CLN1 disease. Fifteen CLN1 disease experts and 39 caregivers responded to the surveys, and 14 experts met to develop consensus-based recommendations. The resulting management recommendations are uniquely informed by family perspectives, due to the inclusion of caregiver and advocate perspectives. A family-centered approach is supported, and individualized, multidisciplinary care is emphasized in the recommendations. Ascertainment of the specific CLN1 disease phenotype (infantile-, late infantile-, juvenile-, or adult-onset) is of key importance in informing the anticipated clinical course, prognosis, and care needs. Goals and strategies should be periodically reevaluated and adapted to patients' current needs, with a primary aim of optimizing patient and family quality of life. (c) 2021 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license (