957 resultados para Goma 7-Step Pathway
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Knoevenagel condensation of 2-acylcyclohexanones or 2-ethoxycarbonylcyclohexanone with either cyanoacetamide or malononitrile followed by silver salt alkylation gave the 5,6,7,8-tetrahydroisoquinolines (3a–i). Chromic acid oxidation of the 5,6,7,8-tetrahydroisoquinolines (3a–i) to the corresponding tetralones (4a–i) followed by sodium borohydride reduction and p-toluenesulphonic acid-catalysed dehydration of the resulting alcohols (5a–i) gave the 5,6-dihydroisoquinolines (6a–i). Reaction of 5,6-dihydroisoquinolines (6a–g) with potassium amide in liquid ammonia gave a mixture of the 1,3-dihydroisoquinolines (7a–g) and the isoquinolines (8a–g). The C-1 unsubstituted 1,2-dihydroisoquinoline (7c) was found to be very unstable. In the case of the 5,6-dihydroisoquinolines (6h and 6i), reaction of potassium amide in liquid ammonia resulted in a mixture of 1-aminoisoquinoline (9) and the isoquinolines (8h and 8i). All the above compounds have been characterised by spectral data. A probable pathway for the formation of the 1,2-dihydroisoquinolines (7a–g) and the isoquinolines (8a–i) is suggested.
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This edition testifies to the broad international reach of the journal, with contributions variously concerned with Arctic Indigenous communities, the Métis of Canada, Native Hawaiians and Māori of Aotearoa (New Zealand). Two articles stress the need to work collaboratively and respectfully with Indigenous populations whilst conducting research. The first, by Gwen Healey, notes the increased interest in health research in the Arctic, particularly with Inuit populations. Healy seeks to add to the growing body of literature concerned with Indigenous ways of knowing by highlighting Inuit concepts that inform an effective Arctic research model. The second, by primary author Peter Hutchinson and a range of co-contributors, highlights the ways in which Métis collaborators working in health developed a participatory Indigenous research method that was unique in that it foregrounded Métis relationships and relationality. In so doing, the researchers were able to give substance to otherwise staid policy statements about the need for good ethical research conduct.
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This edition scales the merlons and embrasures that mark the epistemological barriers that contemporary colonising power continually puts in place. Each article harnesses a critical Indigenous perspective in order to challenge conservative approaches or positions, be they concerned with reconciliation, Indigenous-led research, research tools or the nature of Aboriginal being. The first article, by Barry Judd and Emma Barrow, examines reconciliation discourse within the higher education sector and highlights the ways a normative Anglo-Australian identity militates against genuine ‘whitefella’ attempts to ‘reconcile’. The authors stress the importance of inclusive, institutional practice that serves to decentre Anglo-centrism and which, in turn, brings Indigenous peoples more fully into the fold of Australian university life.
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By using the same current-time (I-t) curves, electrochemical kinetic parameters are determined by two methods, (a) using the ratio of current at a given potential to the diffusion-controlled limiting current and (b) curve fitting method, for the reduction of Cu(II)–CyDTA complex. The analysis by the method (a) shows that the rate determining step involves only one electron although the overall reduction of the complex involves two electrons suggesting thereby the stepwise reduction of the complex. The nature of I-t curves suggests the adsorption of intermediate species at the electrode surface. Under these circumstances more reliable kinetic parameters can be obtained by the method (a) compared to that of (b). Similar observations are found in the case of reduction of Cu(II)–EDTA complex.
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Background Although thermal imaging can be a valuable technology in the prevention and management of diabetic foot disease, it is not yet widely used in clinical practice. Technological advancement in infrared imaging increases its application range. The aim was to explore the first steps in the applicability of high-resolution infrared thermal imaging for noninvasive automated detection of signs of diabetic foot disease. Methods The plantar foot surfaces of 15 diabetes patients were imaged with an infrared camera (resolution, 1.2 mm/pixel): 5 patients had no visible signs of foot complications, 5 patients had local complications (e.g., abundant callus or neuropathic ulcer), and 5 patients had difuse complications (e.g., Charcot foot, infected ulcer, or critical ischemia). Foot temperature was calculated as mean temperature across pixels for the whole foot and for specified regions of interest (ROIs). Results No diferences in mean temperature >1.5 °C between the ipsilateral and the contralateral foot were found in patients without complications. In patients with local complications, mean temperatures of the ipsilateral and the contralateral foot were similar, but temperature at the ROI was >2 °C higher compared with the corresponding region in the contralateral foot and to the mean of the whole ipsilateral foot. In patients with difuse complications, mean temperature diferences of >3 °C between ipsilateral and contralateral foot were found. Conclusions With an algorithm based on parameters that can be captured and analyzed with a high-resolution infrared camera and a computer, it is possible to detect signs of diabetic foot disease and to discriminate between no, local, or difuse diabetic foot complications. As such, an intelligent telemedicine monitoring system for noninvasive automated detection of signs of diabetic foot disease is one step closer. Future studies are essential to confirm and extend these promising early findings.
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Phenylalanine ammonia-lyase (EC 4.3.1.5) was purified to homogeneity from the acetone-dried powders of the mycelial felts of the plant pathogenic fungus Rhizoctonia solani. 2. A useful modification in protamine sulphate treatment to get substantial purification of the enzyme in a single-step is described. 3. The purified enzyme shows bisubstrate activity towards L-phenylalanine and L-tyrosine. 4. It is sensitive to carbonyl reagents and the inhibition is not reversed by gel filtration. 5. The molecular weight of the enzyme as determined by Sephadex G-200 chromatography and sucrose-density-gradient centrifugation is around 330000. 6. The enzyme is made up of two pairs of unidentical subunits, with a molecular weight of 70000 (alpha) and 90000 (beta) respectively. 7. Studies on initial velocity versus substrate concentration have shown significant deviations from Michaelis-Menten kinetics. 8. The double-reciprocal plots are biphasic (concave downwards) and Hofstee plots show a curvilinear pattern. 9. The apparent Km value increases from 0.18 mM to as high as 5.0 mM with the increase in the concentration of the substrate and during this process the Vmax, increases by 2-2.5-fold. 10. The value of Hill coefficient is 0.5. 11. Steady-state rates of phenylalanine ammonia-lyase reaction in the presence of inhibitors like D-phenylalanine, cinnamic, p-coumaric, caffeic, dihydrocaffeic and phenylpyruvic acid have shown that only one molecule of each type of inhibitor binds to a molecule of the enzyme. These observations suggest the involvement of negative homotropic interactions in phenylalanine ammonia-lyase. 12. The enzyme could not be desensitized by treatment with HgCl2, p-chloromercuribenzoic acid or by repeated freezing and thawing.
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Tämän pro gradu -työn tarkoituksena on selvittää tekstin Jer 20:7-13 jumalakuvaa ja muita ”tekstin puhujan” ilmaisemia vuorovaikutussuhteita ja vaihtelevia tunteita. On kuitenkin epäselvää, missä määrin Jeremian kirja tai sen yksittäiset jaksot kuvaavat profeetan persoonaa ja historiallista taustaa. Tekstit voivat kuvata myös muita myöhempiä tilanteita ja asenteita. Tämän tutkimuksen pääasiallinen eksegeettinen metodi on syvyyspsykologinen. Se saattaa pystyä kertomaan jotakin siitä, miten tutkittava teksti peilaa menneisyyden kokemuksellisia kaavoja. Samaan tapaan kuten psykohistoriassa, tutkimus ei yritä tutkia, tulkita tai rekonstruoida tradition tai historian Jeremiaa. Syvyyspsykologinen eksegeesi on tunnistettu jo aiemmin, mutta suomalaisessa tutkimuksessa sitä ei vielä ole sovellettu yksittäisiin teksteihin. Tämän tutkimuksen tutkimusasetelma avaa tekstin sisäisiä ja vaihtelevia vuorovaikutussuhteita eli objektisuhteita. Tutkimus nimittää tätä vuorovaikutussuhteiden analyysiä objektisuhdeanalyysiksi. Se perustuu teologian tohtori, psykoanalyytikko Matti Hyrckin psykoanalyyttiseen suhteessaolon perusmielikuvien teoriaan (SPT), jonka hän esittelee väitöskirjassaan Mielen kuvat Jumalasta (1995). Tekstin Jahve-kuvat on nähtävä objektirepresentaatioina. Nämä vahvasti värittyneet representaatiot ja kuvat kertovat enemmän kokijasta itsestään kuin niistä objekteista, joiden kuviksi ne ovat syntyneet. Käsitys objektien sisäsyntyisyydestä mahdollistaa Hyrckillä objektisuhteiden systematisoinnin ja SPT:n luomisen. Siten emotionaaliset silmälasit on tämän tutkimuksen tekijän mielestä mahdollista valjastaa myös tutkijan käyttöön. Tutkimuksen laaja näkökulmia hakeva teoriaosuus varmistaa tämän. Hermeneuttinen ”kolmen maailman malli” on lukijakeskeisyyteen ja kulttuurihyppyyn arvokas työväline. Jeremian kirja sisältää useita osin runomuotoisia valituksia, joista tutkittava teksti on viimeinen. Valituslaulujen sarja päättyy tutkittavaa tekstiä seuraavaan syntymäpäivän kiroamiseen jakeissa 14-18. Valituksen edellä kontekstina on joitakin kertomuksia Jeremiasta, mutta vasta jakeessa 20:2 Jeremia nimetään profeetaksi. Muuten valittaja on nimetön. Jeremia-kertomusten kehys on tässä toimituksellinen ja valituksen jälkeen seuraa deuteronomistista saarnaa Juudaa ja Jerusalemia vastaan. Tutkimus selvittää jakeiden 7-13 rakennetta, sisältöä ja tulkintaa ensin lähinnä laji- ja kirjallisuus- kriittisesti. Tutkimus osoittaa, että Jeremian valitus noudattaa yksilön valituslaulun kaavaa, mutta ei kuitenkaan yksiselitteisesti taivu lajin usein stereotyyppisiin tarkoituksiin. Suurin syy tähän on tekstin proosa- ja runomuodon vaihtelu ja sisällön hajanaisuus. Edes valituksen ydintä ei voi varmistaa, vaikka valituslaulun nuorimpina osina on tyypillisesti helppo pitää loppupuolen kollektiivisia lisiä. Varsinainen valitus on jakeissa 7-9 ja jakeet 10-13 ovat todennäköisimmin monivaiheinen päätössarja. Tutkimuksen keskeiset objektisuhdeteoreettiset peruskäsitteet sisäinen subjekti ja sisäinen objekti ovat ihmisen tiedostamattoman tason mielikuvia. Varhaisen tilan vuorovaikutusmielikuvien sisäisinä subjekteina ovat Riippuvainen ja Itseriittoinen. Ne ovat vaihtelevissa suhteissa Houkuttajan ja Hallitsijan muotoisia sisäisiä objekteja kohtaan. Myöhäisessä tilassa objekteille on syytä antaa uudet nimet: Vetäytyjä, Vaatija ja Parantaja. Tutkimus etenee osoittamalla tekstin ja SPT:n mukaisen mallin samankaltaisuuksia. Samalla on ollut mahdollista ottaa kantaa myös tekstin saumoihin ja tekstin syntyprosessiin. Tekstin objekti osoittautuu pääosin Hallitsijaksi, sillä Houkuttajan muotoisista jumaluuksista on kollektiivisesti pyritty tekemään pesäeroa Jerusalemin temppelin hävityksestä lähtien. Silti muistoista ja Houkuttajaksikin värittyneistä kaipuun ja pelon muodoista ei päästä eroon. Valituksen alkujakeita 7-9 leimaa Riippuvaisen masennus ja Itseriittoisen häpeä. Jakeissa 11-13 Hallitsijan muotoinen Jahve Sebaot tarjoaa hierarkkista symbioosia. Myöhäistä Vaatijaa ei tutkittavassa tekstissä ole kuin vanhurskaan käsitteenä, joka deuteronomistisessa teologiassa perustuu Jahven sanan kuulemiseen ja lain noudattamiseen. Tutkimus pyrkii osoittamaan, että kaikilla kokemuksilla on jollakin tavalla sekä yhteisöä että yksilöä eheyttäviä tarkoituksia. Kun valitus päättyy sarjaan vakuutuksia ja huipentuu kollektiiviseen ylistyskehotukseen, myös niillä on tarkoitus. Yksi osa tutkimustehtävää on ollut testata psykoanalyyttisen objektisuhdeteoreettisen metodin toimivuutta eksegeettisessä tutkimuksessa. Vaikka tulokset ovat suuntaa antavia, metodi on osoittautunut toimivaksi.
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The structure of the abnormal product 1a formed in the Knoevenagel condensation of 2-carbethoxycyclohexanone and malononitrile has been further confirmed. Oxidation of the tetrahydroisoquinoline 3b using Na2Cr2O-AcOH-H2SO4 gave the keto isoquinoline 3d and the isoquinoline-1-carboxylic acid 5a. The acid chloride of 5a was condensed with diethyl ethoxymagnesiomalonate to afford after decarbethoxylation the methyl ketone 5d which on Baeyer-Villiger oxidation gave a mixture of the acetate 1g and the title compound 1b. The unambiguous synthesis of 1b confirms the structure assigned earlier to the title compound also formed during the partial hydrolysis of the diethoxy compound 1c. Condensation of 2-acetylcyclohexane-1,3-dione with malononitrile gave the quinoline derivative 4c which on ethylation yielded the ketoquinoline 4d. The present studies have confirmed that the quinoline compound 4a is also formed in the condensation of 2-acetylcyclohexanone and cyanoacetamide.
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The reaction of the title complexes (FIG. 1) with N-bromosuccinimide or bromine in chloroform yields isomeric bromo complexes on substitution of the γ-CH carbon proton by bromine. The brominated products have been characterised by ir, pmr, electronic absorption spectra, conductivity and magnetic susceptibility measurements. The linkage isomerisation of the brominated products in chloroform has been shown to depend on the diamine residue.
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This thesis clarifies important molecular pathways that are activated during the cell death observed in Huntington’s disease. Huntington’s disease is one of the most common inherited neurodegenerative diseases, which is primarily inherited in an autosomal dominant manner. HD is caused by an expansion of CAG repeats in the first exon of the IT15 gene. IT15 encodes the production of a Huntington’s disease protein huntingtin. Mutation of the IT15 gene results in a long stretch of polyQ residues close to the amino-terminal region of huntingtin. Huntington’s disease is a fatal autosomal neurodegenerative disorder. Despite the current knowledge of HD, the precise mechanism behind the selective neuronal death, and how the disease propagates, still remains an enigma. The studies mainly focused on the control of endoplasmic reticulum (ER) stress triggered by the mutant huntingtin proteins. The ER is a delicate organelle having essential roles in protein folding and calcium regulation. Even the slightest perturbations on ER homeostasis are effective enough to trigger ER stress and its adaptation pathways, called unfolded protein response (UPR). UPR is essential for cellular homeostasis and it adapts ER to the changing environment and decreases ER stress. If adaptation processes fail and stress is excessive and prolonged; irreversible cell death pathways are engaged. The results showed that inhibition of ER stress with chemical agents are able to decrease cell death and formation of toxic cell aggregates caused by mutant huntingtin proteins. The study concentrated also to the NF-κB (nuclear factor-kappaB) pathway, which is activated during ER stress. NF-κB pathway is capable to regulate the levels of important cellular antioxidants. Cellular antioxidants provide a first line of defence against excess reactive oxygen species. Excess accumulation of reactive oxygen species and subsequent activation of oxidative stress damages motley of vital cellular processes and induce cell degeneration. Data showed that mutant huntingtin proteins downregulate the expression levels of NF-κB and vital antioxidants, which was followed by increased oxidative stress and cell death. Treatment with antioxidants and inhibition of oxidative stress were able to counteract these adverse effects. In addition, thesis connects ER stress caused by mutant huntingtin to the cytoprotective autophagy. Autophagy sustains cellular balance by degrading potentially toxic cell proteins and components observed in Huntington’s disease. The results revealed that cytoprotective autophagy is active at the early points (24h) of ER stress after expression of mutant huntingtin proteins. GADD34 (growth arrest and DNA damage-inducible gene 34), which is previously connected to the regulation of translation during cell stress, was shown to control the stimulation of autophagy. However, GADD34 and autophagy were downregulated at later time points (48h) during mutant huntingtin proteins induced ER stress, and subsequently cell survival decreased. Overexpression GADD34 enhanced autophagy and decreased cell death, indicating that GADD34 plays a critical role in cell protection. The thesis reveales new interesting data about the neuronal cell death pathways seen in Huntington’s disease, and how cell degeneration is partly counteracted by various therapeutic agents. Expression of mutant huntingtin proteins is shown to alter signaling events that control ER stress, oxidative stress and autophagy. Despite that Huntington’s disease is mainly an untreatable disorder; these findings offer potential targets and neuroprotective strategies in designing novel therapies for Huntington’s disease.