15 research outputs found

    Electron transparent nanotubes reveal crystallization pathways in confinement

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    The cylindrical pores of track-etched membranes offer excellent environments for studying the effects of confinement on crystallization as the pore diameter is readily varied and the anisotropic morphologies can direct crystal orientation. However, the inability to image individual crystals in situ within the pores in this system has prevented many of the underlying mechanisms from being characterized. Here, we study the crystallization of calcium sulfate within track-etched membranes and reveal that oriented gypsum forms in 200 nm diameter pores, bassanite in 25–100 nm pores and anhydrite in 10 nm pores. The crystallization pathways are then studied by coating the membranes with an amorphous titania layer prior to mineralization to create electron transparent nanotubes that protect fragile precursor materials. By visualizing the evolutionary pathways of the crystals within the pores we show that the product single crystals derive from multiple nucleation events and that orientation is determined at early reaction times. Finally, the transformation of bassanite to gypsum within the membrane pores is studied using experiment and potential mean force calculations and is shown to proceed by localized dissolution/reprecipitation. This work provides insight into the effects of confinement on crystallization processes, which is relevant to mineral formation in many real-world environments

    Update of EULAR recommendations for the treatment of systemic sclerosis

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    The aim was to update the 2009 European League against Rheumatism (EULAR) recommendations for the treatment of systemic sclerosis (SSc), with attention to new therapeutic questions. Update of the previous treatment recommendations was performed according to EULAR standard operating procedures. The task force consisted of 32 SSc clinical experts from Europe and the USA, 2 patients nominated by the pan-European patient association for SSc (Federation of European Scleroderma Associations (FESCA)), a clinical epidemiologist and 2 research fellows. All centres from the EULAR Scleroderma Trials and Research group were invited to submit and select clinical questions concerning SSc treatment using a Delphi approach. Accordingly, 46 clinical questions addressing 26 different interventions were selected for systematic literature review. The new recommendations were based on the available evidence and developed in a consensus meeting with clinical experts and patients. The procedure resulted in 16 recommendations being developed (instead of 14 in 2009) that address treatment of several SSc-related organ complications: Raynaud's phenomenon (RP), digital ulcers (DUs), pulmonary arterial hypertension (PAH), skin and lung disease, scleroderma renal crisis and gastrointestinal involvement. Compared with the 2009 recommendations, the 2016 recommendations include phosphodiesterase type 5 (PDE-5) inhibitors for the treatment of SSc-related RP and DUs, riociguat, new aspects for endothelin receptor antagonists, prostacyclin analogues and PDE-5 inhibitors for SSc-related PAH. New recommendations regarding the use of fluoxetine for SSc-related RP and haematopoietic stem cell transplantation for selected patients with rapidly progressive SSc were also added. In addition, several comments regarding other treatments addressed in clinical questions and suggestions for the SSc research agenda were formulated. These updated data-derived and consensus-derived recommendations will help rheumatologists to manage patients with SSc in an evidence-based way. These recommendations also give directions for future clinical research in SSc

    Analysis of shift time structure during tree culture cultivation with brush cutters

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    Together with the growth of young trees cultivation carried out by the National Forestry Board it became necessary to mechanize the works that would increase their efficiency with equally high quality. Recognition and optimalization of worktime structure of brush cutter operators during cultivation is of great practical importance in this context. Technological improvement of cultivation in the analysed experiment applied a square method (fig. 1), while technical rationalisation consisted in cutting around young trees. The worktime structure of the described workstand was defined with the help of a working day photography being taken for three days for four workers. Next the measured time data were classified according to a scheme from fig. l. A relatively high fraction of resting time and maintenance of the brush cutter in a workshift proved that an exploitation shift time coefficient of effectiveness was 0.61. On the basis of differences between effective worktime and rest distributions as well as technological stand-still and everyday maintenance it was presumed that the cause of frequent work breaks were repeated repairs of brush cutters.(fig. 6). High value of coefficient of operating time efficiency (0.93) proved the optimum choice of the applied technology. The work efficiency assumed for the experiment - three times higher than for a hand tool -indicates that it is necessary to turn to a hand-machine level of cultivating.Wobec dużego rozmiaru prac pielęgnacyjnych realizowanych przez Lasy Państwowe niezbędna jest ich mechanizacja, podnosząca wydajność przy niezmienionej jakości wykonania. Poznanie i optymalizacja struktury czasu pracy operatorów wykaszarek spalinowych przy wykonywaniu pielęgnacji upraw ma w tym kontekście duże znaczenie praktyczne. Racjonalizacja technologii pielęgnacji upraw w analizowanym doświadczeniu polegała na stosowaniu metody kwadratu (rys. 1), zaś techniki pracy na obkaszaniu drzewek (rys. 2). Strukturę czasu pracy opisywanego stanowiska określono na podstawie fotografii dnia roboczego prowadzonej dla czterech robotników przez trzy dni. Następnie sklasyfikowano pomierzone czasy wg schematu z tab 1. Stosunkowo duży udział w zmianie roboczej czasów odpoczynków i napraw urządzenia tnącego (rys. 3) spowodował, że współczynnik wykorzystania eksploatacyjnego czasu zmiany wyniósł 0,61. Na podstawie różnic rozkładów efektywnego czasu pracy i odpoczynków oraz czasów przestojów technologicznych i codziennej obsługi maszyn wnioskowano, że przyczyną częstych przerw w pracy jest wielokrotna naprawa urządzenia tnącego (rys. 5). Zależność tą potwierdzono, charakteryzując istniejący związek jako zależność liniową (rys. 6). Wysoka wartość współczynnika wykorzystania czasu operacyjnego - 0,93 - potwierdziła optymalny dobór zastosowanej technologii prac. Określona w doświadczeniu wydajność prac - trzykrotnie wyższa w porównaniu z narzędziem ręcznym, wskazuje na konieczność przejścia na poziom ręczno-maszynowy wykonywania pielęgnacji upraw

    Subunit composition of nicotinic receptors in monkey striatum : effect of treatments with 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine or L-DOPA

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    Nicotinic acetylcholine receptors (nAChRs) represent an important modulator of striatal function both under normal conditions and in pathological states such as Parkinson's disease. Because different nAChR subtypes may have unique functions, immunoprecipitation and ligand binding studies were done to identify their subunit composition. As in the rodent, alpha2, alpha4, alpha6, beta2, and beta3 nAChR subunit immunoreactivity was identified in monkey striatum. However, distinct from the rodent, the present results also revealed the novel presence of alpha3 nAChR subunit-immunoreactivity in this same region, but not that for alpha5 and beta4. Relatively high levels of alpha2 and alpha3 subunits were also identified in monkey cortex, in addition to alpha4 and beta2. Experiments were next done to determine whether striatal subunit expression was changed with nigrostriatal damage. 1-Methyl-4-phenyl- 1,2,3,6-tetrahydropyridine treatment decreased alpha6 and beta3 subunit immunoreactivity by similar to80% in parallel with the dopamine transporter, suggesting that they are predominantly expressed on nigrostriatal dopaminergic projections. In contrast, alpha3, alpha4, and beta2 subunit immunoreactivity was decreased similar to50%, whereas alpha2 was not changed. These data, together with those from dual immunoprecipitation and radioligand binding studies ([H-3] cytisine, I-125-alpha-bungarotoxin, and I-125-alpha-conotoxin MII) suggest the following: that alpha6beta2beta3, alpha6alpha4beta2beta3, and alpha3beta2* nAChR subtypes are present on dopaminergic terminals and that the alpha4beta2 subtype is localized on both dopaminergic and nondopaminergic neurons, whereas alpha2beta2* and alpha7 receptors are localized on nondopaminergic cells in monkey striatum. Overall, these results suggest that drugs targeting non-alpha7 nicotinic receptors may be useful in the treatment of disorders characterized by nigrostriatal dopaminergic damage, such as Parkinson's disease

    N-acetylcysteine normalizes neurochemical changes in the glutathione-deficient schizophrenia mouse model during development.

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    BACKGROUND: Glutathione (GSH) is the major cellular redox-regulator and antioxidant. Redox-imbalance due to genetically impaired GSH synthesis is among the risk factors for schizophrenia. Here we used a mouse model with chronic GSH deficit induced by knockout (KO) of the key GSH-synthesizing enzyme, glutamate-cysteine ligase modulatory subunit (GCLM).¦METHODS: With high-resolution magnetic resonance spectroscopy at 14.1 T, we determined the neurochemical profile of GCLM-KO, heterozygous, and wild-type mice in anterior cortex throughout development in a longitudinal study design.¦RESULTS: Chronic GSH deficit was accompanied by an elevation of glutamine (Gln), glutamate (Glu), Gln/Glu, N-acetylaspartate, myo-Inositol, lactate, and alanine. Changes were predominantly present at prepubertal ages (postnatal days 20 and 30). Treatment with N-acetylcysteine from gestation on normalized most neurochemical alterations to wild-type level.¦CONCLUSIONS: Changes observed in GCLM-KO anterior cortex, notably the increase in Gln, Glu, and Gln/Glu, were similar to those reported in early schizophrenia, emphasizing the link between redox imbalance and the disease and validating the model. The data also highlight the prepubertal period as a sensitive time for redox-related neurochemical changes and demonstrate beneficial effects of early N-acetylcysteine treatment. Moreover, the data demonstrate the translational value of magnetic resonance spectroscopy to study brain disease in preclinical models

    alpha-conotoxins as tools for the elucidation of structure and function of neuronal nicotinic acetylcholine receptor subtypes

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    Cone snails comprise approximate to 500 species of venomous molluscs, which have evolved the ability to generate multiple toxins with varied and often exquisite selectivity. One class, the alpha-conotoxins, is proving to be a powerful tool for the differentiation of nicotinic acetylcholine receptors (nAChRs). These comprise a large family of complex subtypes, whose significance in physiological functions and pathological conditions is increasingly becoming apparent. After a short introduction into the structure and diversity of nAChRs, this overview summarizes the identification and characterization of alpha-conotoxins with selectivity for neuronal nAChR subtypes and provides examples of their use in defining the compositions and function of neuronal nAChR subtypes in native vertebrate tissues
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