4,968 research outputs found

    New Year\u27s Resolution

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    Some Studies in the Synthesis of Medium Ring Ketones

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    Synthetic routes to 9 and 10 membered ring systems have been investigated as follows: Biroh reduction of napalene yields isotetralin (1:4:5:8 tetrahydronaph halene) which has been converted through its mono epoxide (9:10-oxido: Delta2:6 hexahydronaplthalene) to trans Delta 2:6 hexahydronaphalene-9:10-diol and this substance has been cleaved by means of lead tetrancetate to cyclodeca-3:8 dien-1:6-dione. The product has been characterised as its bis-2:4-dinotrophenylhydrazone. Attempts to introduce further unsaturation into the ring were unsuccessful. A similar series of reactions was carried out on indane, and yielded in turn, 4:7-dihydro-8:9 oxidoindene, the corresponding diol, Delta5:6 hexa-hydroindene-8:9-diol and cyclonon-7en-1:5-dione. The structure of this end product was rigorously established by its reduction under special conditions to cyolononan-1:5-diol. This product was isolated as a mixture of stereoisomers, one of which was found to be identical with an authentic sample kindly supplied by Professor V. Prolog of Zurich. Under different conditions the reduction proceeded anomalously. In an attempt to isomerise the double bond into conjugation with one of the carbonyl functions, the ene dione was treated with ethanolic potassium acetate. The product was not the expected conjugated dione. An exhaustive investigation, employing both chemical and spectroscopic methods has shown that the potassium acetate treatment promotes a transannular aldol condensation yielding initially 4:5:6:7-tetrahydroinden-7-one which dimerises fairly rapidly. The structure of the dimer has been tentatively assigned on the basis of its proton magnetic resonance spectrum

    A novel 3D human glioblastoma cell culture system for modeling drug and radiation responses

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    Background. Glioblastoma (GBM) is the most common primary brain tumor, with dismal prognosis. The failure of drug–radiation combinations with promising preclinical data to translate into effective clinical treatments may relate to the use of simplified 2-dimensional in vitro GBM cultures. Methods. We developed a customized 3D GBM culture system based on a polystyrene scaffold (Alvetex) that recapitulates key histological features of GBM and compared it with conventional 2D cultures with respect to their response to radiation and to molecular targeted agents for which clinical data are available. Results. In 3 patient-derived GBM lines, no difference in radiation sensitivity was observed between 2D and 3D cultures, as measured by clonogenic survival. Three different molecular targeted agents, for which robust clinical data are available were evaluated in 2D and 3D conditions: (i) temozolomide, which improves overall survival and is standard of care for GBM, exhibited statistically significant effects on clonogenic survival in both patient-derived cell lines when evaluated in the 3D model compared with only one cell line in 2D cells; (ii) bevacizumab, which has been shown to increase progression-free survival when added to standard chemoradiation in phase III clinical trials, exhibited marked radiosensitizing activity in our 3D model but had no effect on 2D cells; and (iii) erlotinib, which had no efficacy in clinical trials, displayed no activity in our 3D GBM model, but radiosensitized 2D cells. Conclusions. Our 3D model reliably predicted clinical efficacy, strongly supporting its clinical relevance and potential value in preclinical evaluation of drug–radiation combinations for GBM

    Hyperpyrexia in rheumatism: considered chiefly from a clinical standpoint

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    The main conclusions I would draw from the consideration of the whole subject of Hyperpyrexia in Rheumatism are these:- 1. That the condition is more prone to occur in the warmer months of the year and apparently with greater frequency in certain years. 2. That while it is very difficult to estimate at all accurately the frequency of its occurrence, pro¬ bably this is about .bf amongst adult cases of Rheumatism. 3. That the occurrence of Hyperpyrexia in Rheumatism is practically confined to cases of this disease in persons over 14 years of age. 4. That the rare instances of hyperpyrexia which occur under that age are in cases of Rheumatism which present the adult type of the disease. 5. That the absence of Hyperpyrexia from Rheumatism in children is probably to be explained as the result of the type Rheumatism assumes in them rather than a mere question of the age of the sufferer. 6. That males shew a much greater proclivity to the condition than females, which may possibly be associated with the greater strain habitually put upon their thermo-taxic mechanism. 7. That the condition is most apt to occur in "first attacks" of Rheumatism. 8. That persons who have suffered from the condition would probably be apt to have a recurrence of it in any subsequent attack of the disease (although no case of such recurrence has as yet been published). 9. That it may ensue at any stage in an attack of Rheumatism, but probably the second week is the most common period of its occurrence. 10. That it may arise in even mild cases of Rheumatism, severe rheumatic symptoms being essential to its occurrence. 11. That the onset of Hyperpyrexia, while occasionally without warning, has usually premonitory symptoms the chief of which is Delirium. 12. That cases of true Rheumatism shewing persistence of the pyrexia in spite of full doses of the Salicyl compounds should be most carefully watched since Hyper¬ pyrexia frequently ensues in such instances. 13. That sudden cessation of the articular pains without coincident fall of temperature should lead to the suspicion of Hyperpyrexia, especially if attended also by the cessation of sweating. 14. That MacLagan's hypothesis"that Hyperpyrexia is due to; paresis of the Heat -inhibiting mechanism from exhaustion in its attempt to control the exeessiva heat production of Rheumatism is the most feasible theory yet put forward in explanation of the condition satisfactorily accounting for the more frequent occurrence of Hyperpyrexia in Adults than in children. 15. That the absence of Rheumatic Hyperpyrexia in children is a strong argument against the view that this condition is due to visceral complications, since, it is especially in children that these visceral manifestations occur and it is just in those cases that Hyperpyrexia is not found. 16. That in view of the resemblance in several respects between Rheumatic Hyperpyrexia and. "Diabetic Coma", farther investigation of this subject might possibly throw fresh light upon the pathogenesis of both conditions. 17. That while the mortality of Rheumatism is only about 3%, Hyperpyrexia is probably one of the most important immediate causes of death in this disease. 18. That the mortality of Hyperpyretic cases is very high - probably over 50^, but statistics are very variable because - 19. The mortality is greater the higher the temperature before treatment is begun: and 20. It is also greater amongst cases treated by means of antipyretic drugs alone. 21. That the treatment by the application of cold in one of its various forms is the only justifiable method in cases of Hyperpyrexia in Rheumatism. 22. That this should be adopted even in cases apparently: moribund and even although visceral complications may be present. 23. That while there may possibly be some risk of congestion of internal organs as a result of this method of treatment, this does not justify the neglect of what is practically the only remedy for an otherwise fatal condition. 24. That the greatest care should be taken to prevent collapse ensuing in the patient as a result of the treatment by cold which should be stopped entirely before temperature falls to normal. 25. That antipyretic drugs, while practically useless in the treatment of Hyperpyrexia when present, may perhaps be of some service in preventing a recurrence of this after the temperature has once been reduced by means of cold. 26. That in obstinate cases of Recurrent Hyperpyrexia the method of treatment by "Disintoxication of the Blood" adopted by Barre may probably be of service as an adjuvant to the treatment by means of cold. 27. That a greater attention should be paid to the Prophylaxis of Rheumatic Hyperpyrexia,, and that more prominence should be given to the advantage of commencing treatment by cold at an early stage before excessive temperatures are attained; in other words, the general condition of the patient rather than the mere height of his temperature Should be the determining factor for commencing the treatment by cold. 28. That early and complete subjection of the patient to Anti-rheumatic treatment would probably have some influence in preventing the occurrence of Hyperpyrexia

    Genomic analysis of the role of transcription factor C/EBPδ in the regulation of cell behaviour on nanometric grooves

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    C/EBPδ is a tumour suppressor transcription factor that induces gene expression involved in suppressing cell migration. Here we investigate whether C/EBPδ-dependent gene expression also affects cell responses to nanometric topology. We found that ablation of the C/EBPδ gene in mouse embryonal fibroblasts (MEFs) decreased cell size, adhesion and cytoskeleton spreading on 240 nm and 540 nm nanometric grooves. ChIP-SEQ and cDNA microarray analyses demonstrated that many binding sites for C/EBPδ, and the closely related C/EBPβ, exist throughout the mouse genome and control the upregulation or downregulation of many adjacent genes. We also identified a group of C/EBPδ-dependent, trans-regulated genes, whose promoters contained no C/EBPδ binding sites and yet their activity was regulated in a C/EBPδ-dependent manner. These genes include signalling molecules (e.g. SOCS3), cytoskeletal components (Tubb2, Krt16 and Krt20) and cytoskeletal regulators (ArhGEF33 and Rnd3) and are possibly regulated by cis-regulated diffusible mediators, such as IL6. Of particular note, SOCS3 was shown to be absolutely required for efficient cell spreading and contact guidance on 240 nm and 540 nm nanometric grooves. C/EBPδ is therefore involved in the complex regulation of multiple genes, including cytoskeletal components and signalling mediators, which influence the nature of cell interactions with nanometric topology

    An overview of recent advances of the catalytic selective oxidation of ethane to oxygenates

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    The selective partial oxidation of short chain alkanes is a key challenge within catalysis research. Direct ethane oxidation to oxygenates is a difficult aim, but potentially rewarding, and it could lead to a paradigm shift in the supply chain of several bulk chemicals. Unfortunately, low C–H bond reactivity and kinetically labile products are just some reasons affecting the development and commercialisation of such processes. Research into direct ethane oxidation is therefore disparate, with approaches ranging from oxidation in the gas phase at high temperatures to enzyme catalysed hydroxylation under ambient conditions. Furthermore, in overcoming the barrier posed by the chemically inert C–H bond a range of oxidants have been utilised. Despite years of research, this remains an intriguing topic from both academic and commercial perspectives. Herein we describe some recent developments within the field of catalytic ethane oxidation focusing on the formation of oxygenated products, whilst addressing the key challenges which are still to be overcome

    Community experiences of organised crime in Scotland

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    The research explored community experiences of serious organised crime in Scotland (SOC). The report provides information on the nature and extent of the impact of SOC on everyday life in the community, as well as offering suggestions for policy development. The study sought to answer the following questions: 1)What are the relationships that exist between SOC and communities in Scotland? 2)What are the experiences and perceptions of residents, stakeholders and organisations of the scope and nature of SOC within their local area? and 3)How does SOC impact on community wellbeing, and to what extent can the harms associated with SOC be mitigated

    Survey of selected tufa forming sites in Staffordshire, UK

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    The report details a short survey of tufa forming sites in Staffordshire, commissioned by the Staffordshire Wildlife trust. Its principal aim was to determine which tufa sites could be classed as ‘H7220 Petrifying springs with tufa formation (Cratoneurion)’ under the Habitats Directive. Recommendations are also made for future site enhancements. Water chemistry data collected from these sites is compared to data from similar tufa forming springs across the UK
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