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Profound Differences (profound + difference)
Selected AbstractsConservation of DNA methylation in dipteran insectsINSECT MOLECULAR BIOLOGY, Issue 2 2004J. Marhold Abstract DNA methylation is a central mechanism of epigenetic regulation. Whereas vertebrate DNA methylation requires at least four different DNA methyltransferases, Drosophila melanogaster only utilizes a single, Dnmt2-like enzyme. This profound difference has raised the question of the evolutionary significance of the Drosophila methylation system. We have now identified Dnmt2-like open reading frames in the genome sequences of Drosophila pseudoobscura and Anopheles gambiae. These genes represent the only candidate DNA methyltransferases in their respective genomes. Consistent with a catalytic activity of Dnmt2 proteins, we could also demonstrate low but significant levels of DNA methylation in genomic DNA from these species. Lastly, we were also able to detect highly conserved Dnmt2-like open reading frames and concomitant DNA methylation in several additional Drosophila species, which suggests that Dnmt2-mediated DNA methylation has been conserved over a considerable evolutionary distance. [source] Targeting tumor metabolism with 2-deoxyglucose in patients with castrate-resistant prostate cancer and advanced malignanciesTHE PROSTATE, Issue 13 2010Mark Stein Abstract BACKGROUND A profound difference between cancer and normal tissues is the preferential utilization of glycolysis by cancer cells. To translate this paradigm in the clinic, we completed a phase I study of 2-deoxyglucose (2DG), and assessed 2DG uptake with fluorodeoxyglucose (FDG) positron emission tomography (PET) and the autophagy substrate p62 as a marker of 2DG resistance. METHODS Patients received 2DG orally on days 1,14 of a 21-day cycle in cohorts of three in a dose-escalating manner. Correlative assessments included PET scans at baseline and day 2 and p62 protein in peripheral blood mononuclear cells as a potential marker of 2DG resistance. RESULTS The dose of 45,mg/kg was defined as the recommended phase II dose, secondary to dose-limiting toxicity of grade 3 asymptomatic QTc prolongation at a dose of 60,mg/kg. PK evaluation of 2DG revealed linear pharmacokinetics with Cmax 45,µg/ml (277,µM), 73.7,µg/ml (449,µM), and 122,µg/ml (744,µM) in dose levels 30, 45, and 60,mg/kg, respectively. Five of eight patients assessed with FDG-PET scanning demonstrated decreased FDG uptake by day 2 of therapy, suggesting competition of 2DG with FDG. Five of six patients assessed for p62 had a decrease in p62 at 24,hr. CONCLUSIONS These data support the safety of 2DG, defined 2DG PK, demonstrated the effect of 2DG on FDG-PET imaging, and demonstrated the feasibility of assessment of p62 as an autophagic resistance marker. These data support future studies of 2DG alone or in combination with approaches to abrogate autophagy. Prostate 70: 1388,1394, 2010. © 2010 Wiley-Liss, Inc. [source] Impact of membrane solid,liquid separation on design of biological nutrient removal activated sludge systemsBIOTECHNOLOGY & BIOENGINEERING, Issue 6 2005M. Ramphao Abstract Installing membranes for solid,liquid separation into biological nutrient removal (BNR) activated sludge (AS) systems makes a profound difference not only in the design of the BNR system itself, but also in the design approach for the whole wastewater treatment plant (WWTP). In multizone BNR systems with membranes in the aerobic reactor and fixed volumes for the anaerobic, anoxic, and aerobic zones (i.e., fixed volume fractions), the mass fractions can be controlled (within a range) with the interreactor recycle ratios. This zone mass fraction flexibility is a significant advantage in membrane BNR systems over conventional BNR systems with SSTs, because it allows for changing of the mass fractions to optimize biological N and P removal in conformity with influent wastewater characteristics and the effluent N and P concentrations required. For PWWF/ADWF ratios in the upper range (fq , 2.0), aerobic mass fractions in the lower range (fmaer < 0.60), and high (usually raw) wastewater strengths, the indicated mode of operation of MBR BNR systems is as extended aeration WWTPs. Although the volume reduction compared with equivalent conventional BNR systems with secondary settling tanks is not as large (40% to 60%), the cost of the membranes can be offset against sludge thickening and stabilization costs. Moving from a flow-unbalanced raw wastewater system to a flow-balanced (fq = 1), low (usually settled) wastewater strength system can double the ADWF capacity of the biological reactor, but the design approach of the WWTP changes from extended aeration to include primary sludge stabilization. The cost of primary sludge treatment then has to be paid from the savings from the increased WWTP capacity. © 2005 Wiley Periodicals, Inc. [source] How Does the Trans,Cis Photoisomerization of Azobenzene Take Place in Organic Solvents?CHEMPHYSCHEM, Issue 5 2010Giustiniano Tiberio Dr. Abstract The trans,cis photoisomerization of azobenzene-containing materials is key to a number of photomechanical applications, but the actual conversion mechanism in condensed phases is still largely unknown. Herein, we study the isomerization in a vacuum and in various solvents via a modified molecular dynamics simulation adopting an ab initio torsion,inversion force field in the ground and excited states, while allowing for electronic transitions and a stochastic decay to the fundamental state. We determine the trans,cis photoisomerization quantum yield and decay times in various solvents (n -hexane, anisole, toluene, ethanol, and ethylene glycol), and obtain results comparable with experimental ones where available. A profound difference between the isomerization mechanism in vacuum and in solution is found, with the often neglected mixed torsional,inversion pathway being the most important in solvents. [source] Europe and the Crisis in Scientific VocationsEUROPEAN JOURNAL OF EDUCATION, Issue 4 2005BERNARD CONVERT During the 1990s, the number of students enrolling in science subjects at universities was declining each year in Germany, France, Italy, amongst other countries. These decreases are too readily attributed to a general disaffection caused by the image that younger generations have of scientific studies: they are seen as being the most ,difficult'. This explanation is true but not sufficient. Over and above the similarities that can be seen between European countries , which stem from the fact that they are simultaneously experiencing strong growth in and democratisation of their student populations ,, profound differences continue to exist, resulting in apparently similar effects, but with very different causes. Not only do higher education structures taken as a whole remain very different despite the Bologna process, but more fundamentally, the very meaning of the higher education system within each national society, its relationship with employment, and its position in individuals' personal career paths all vary. A comparison between Germany, Italy and France shows three ideal types of relationship between training and employment and three ways of explaining symptoms that appear similar. [source] Localization of the A kinase anchoring protein AKAP79 in the human hippocampusEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 4 2000Attila Sík Abstract The phosphorylation state of the proteins, regulated by phosphatases and kinases, plays an important role in signal transduction and long-term changes in neuronal excitability. In neurons, cAMP-dependent protein kinase (PKA), protein kinase C (PKC) and calcineurin (CN) are attached to a scaffold protein, A kinase anchoring protein (AKAP), thought to anchor these three enzymes to specific sites of action. However, the localization of AKAP, and the predicted sites of linked phosphatase and kinase activities, are still unknown at the fine structural level. In the present study, we investigated the distribution of AKAP79 in the hippocampus from postmortem human brains and lobectomy samples from patients with intractable epilepsy, using preembedding immunoperoxidase and immunogold histochemical methods. AKAP79 was found in the CA1, presubicular and subicular regions, mostly in pyramidal cell dendrites, whereas pyramidal cells in the CA3, CA2 regions and dentate granule cells were negative both in postmortem and in surgical samples. In some epileptic cases, the dentate molecular layer and hilar interneurons also became immunoreactive. At the subcellular level, AKAP79 immunoreactivity was present in postsynaptic profiles near, but not attached to, the postsynaptic density of asymmetrical (presumed excitatory) synapses. We conclude that the spatial selectivity for the action of certain kinases and phosphatases regulating various ligand- and voltage-gated channels may be ensured by the selective presence of their anchoring protein, AKAP79, at the majority of glutamatergic synapses in the CA1, but not in the CA2/CA3 regions, suggesting profound differences in signal transduction and long-term synaptic plasticity between these regions of the human hippocampus. [source] Natural killer T-cell characterization through gene expression profiling: an account of versatility bridging T helper type 1 (Th1), Th2 and Th17 immune responsesIMMUNOLOGY, Issue 1 2008Marcus Niemeyer Summary Natural killer T (NKT) cells constitute a distinct lymphocyte lineage at the interface between innate and adaptive immunity, yet their role in the immune response remains elusive. Whilst NKT cells share features with other conventional T lymphocytes, they are unique in their rapid, concomitant production of T helper type 1 (Th1) and Th2 cytokines upon T-cell receptor (TCR) ligation. In order to characterize the gene expression of NKT cells, we performed comparative microarray analyses of murine resting NKT cells, natural killer (NK) cells and naïve conventional CD4+ T helper (Th) and regulatory T cells (Treg). We then compared the gene expression profiles of resting and alpha-galactosylceramide (,GalCer)-activated NKT cells to elucidate the gene expression signature upon activation. We describe here profound differences in gene expression among the various cell types and the identification of a unique NKT cell gene expression profile. In addition to known NKT cell-specific markers, many genes were expressed in NKT cells that had not been attributed to this population before. NKT cells share features not only with Th1 and Th2 cells but also with Th17 cells. Our data provide new insights into the functional competence of NKT cells which will facilitate a better understanding of their versatile role during immune responses. [source] How different are luminal A and basal breast cancers?INTERNATIONAL JOURNAL OF CANCER, Issue 6 2009François Bertucci Abstract Heterogeneity of breast cancer makes its evolution difficult to predict, and its treatment far from being optimal. At least 5 main molecular subtypes exist. Two major subtypes are luminal A and basal subtypes, which have opposite features, notably survival. To characterize these 2 subtypes better, with the hope of better understanding their different biology and clinical outcome, we have profiled a series of 138 tumours (80 luminal A and 58 basal) using Affymetrix whole-genome DNA microarrays. We have identified 5,621 probe sets as differentially expressed between the 2 subtypes in our series. These differences were validated in 6 independent public series (more than 600 tumours) profiled using different DNA microarrays platforms. Analysis of functions and pathways related to these probe sets, and the extent of the observed differences, confirmed that the 2 subtypes represent very distinct entities. Genes associated with proliferation, cell cycle, cell motility, angiogenesis, and NFkB signalling were overexpressed in basal tumours. Genes involved in fatty acid metabolism, TGFB signalling, and oestrogen receptor (ER) signalling were overexpressed in luminal A samples. Half of the genes overexpressed in luminal tumours contained ER-binding sites. The number of differentially expressed genes was as high as the set of genes discriminating 2 cancers of different anatomical origin (breast and colon) or discriminating acute myeloid and lymphoid leukaemia. We provide a comprehensive list of genes/pathways that define potential diagnostic, prognostic and therapeutic targets for these 2 subtypes, which should be treated differently given the profound differences observed at the molecular level. © 2008 Wiley-Liss, Inc. [source] Are German, Japanese and Anglo-Saxon Strategic Decision Styles Still Divergent in the Context of Globalization?*JOURNAL OF MANAGEMENT STUDIES, Issue 6 2005Chris Carr abstract Issues of globalization and divergence in terms of national systems and cultures are equally contentious, yet equally important, in the context of increasing cross-continental co-operation. This article investigates comparative strategic decision styles in Britain, the USA, Germany and Japan. An industry at an advanced stage in terms of globalization, vehicle components manufacture, was selected in order to explore the extent of convergence and whether this has changed. Between 1989 and 1998, field case studies were made of 100 strategic investment decisions (SIDs) by manufacturers in these four countries. Longitudinal judgements were supplemented by earlier comparative strategy field research carried out in 60 suppliers between 1980 and 1983, and two longitudinal case studies, one from the UK and one from Japan, interviewed throughout both these periods and again in 2002. Two competing hypotheses, derived from rich research literatures, are investigated. The first (H1) suggests that national institutional and cultural factors exert profound differences, and should therefore be afforded more significance as globalization proceeds further. The second (H2) is apparently contradictory and emphasizes that institutions and organizations are likely to respond to convergence pressures, spurred by global capital markets and competition on the one hand, and a diffusion of ,professional management' practices on the other. Japanese firms generally, and German family firms in particular, were still found to exhibit deep-rooted differences from the Anglo-Saxon model, which appears to confirm H1. However study of German public companies reveals that their strategic approaches are far less divergent from what is now an increasingly consistent Anglo-Saxon model than they were a decade ago, which appears to confirm the competing hypothesis H2. [source] Shoreline tufa and tufaglomerate from Pleistocene Lake Bonneville, Utah, USA: stable isotopic and mineralogical records of lake conditions, processes, and climate,JOURNAL OF QUATERNARY SCIENCE, Issue 1 2005Stephen T. Nelson Abstract Shoreline carbonate deposits of Pleistocene Lake Bonneville record the conditions and processes within the lake, including the evaporative balance as well as vertical and lateral chemical and isotopic gradients. Tufas (swash-zone) and tufaglomerates (cemented, subaqueous colluvium or beachrock) on multiple, well-developed shorelines near the Silver Island Range, Utah, also present an opportunity to examine physicochemical lake processes through time. Three shorelines are represented by carbonate deposits, including the 23,20,ka Stansbury stage, 15,14.5,ka Bonneville stage, and 14.5,14,ka Provo stage. Mean ,18OVSMOW values of all three shorelines are statistically indistinguishable (,,,27,±,1,), when a few Bonneville samples of unusual composition are neglected. However, differences in primary carbonate mineralogy indicate that the correspondence is an artefact of the different fractionation factors between calcite or aragonite and water. Second, in order to sustain a much smaller, shallower lake during the colder Stansbury stage, the climate must have also been relatively dry. Third, ,18O values in tufa are higher than tufaglomerate by ,,,0.5,, consistent with greater evaporative enrichment of lake water in the swash zone. Fourth, mean ,13C values for the Provo, Stansbury and Bonneville shorelines (4.4, 5.0 and 5.2,, respectively) show that carbon species were dominated by atmospheric exchange, with the variations produced by differences in the oxidation of organic matter. Comparisons of shoreline carbonates with deep-lake marls of the same approximate age indicate that shoreline carbonate was much higher in ,13C and ,18O values (both ,,2.5,) during Bonneville time, whereas isotopic differences were minor (both ,,1,) in Stansbury time. In particular, the Bonneville stage may have sustained large vertical or lateral isotopic gradients due to evaporative enrichment effects on ,18O values. In contrast, the lake during the much shallower Stansbury stage may have been well mixed. Differences in the primary mineralogy (Stansbury and Bonneville, aragonite,>,calcite; Provo, calcite,>,aragonite) reflect profound differences in lake chemistry in terms of open versus closed-basin lakes. The establishment of a continuous outlet during Provo time probably reduced the Mg2+/Ca2+ ratio of lake water. Curiously, regardless of primary mineralogy, tufaglomerate cements are enriched in Na+ and Cl, and depleted in Mg2+ relative to capping tufa of the same age. This probably reflects vital or kinetic effects in the swash zone (tufa). We suspect that ,abiotic' effects may have been important in the dark pore space of developing tufaglomerate, where the absence of light suppressed photosynthesis. Copyright © 2005 John Wiley & Sons, Ltd. [source] Candida albicans lacking the frataxin homologue: a relevant yeast model for studying the role of frataxinMOLECULAR MICROBIOLOGY, Issue 2 2004Renata Santos Summary We cloned the CaYFH1 gene that encodes the yeast frataxin homologue in Candida albicans. CaYFH1 was expressed in ,yfh1 Saccharomyces cerevisiae cells, where it compensated for all the phenotypes tested except for the lack of cytochromes. Double ,Cayfh1/,Cayfh1 mutant had severe defective growth, accumulated iron in their mitochondria, lacked aconitase and succinate dehydrogenase activity and had defective respiration. The reductive, siderophore and haem uptake systems were constitutively induced and the cells excreted flavins, thus behaving like iron-deprived wild-type cells. Mutant cells accumulated reactive oxygen species and were hypersensitive to oxidative stress, but not to iron. Cytochromes were less abundant in mutants than in wild-type cells, but this did not result from defective haem synthesis. The low cytochrome concentration in mutant cells was comparable to that of iron-deprived wild-type cells. Mitochondrial iron was still available for haem synthesis in ,Cayfh1/,Cayfh1 cells, in contrast to S. cerevisae,yfh1 cells. CaYFH1 transcription was strongly induced by iron, which is consistent with a role of CaYfh1 in iron storage. Iron also regulated transcription of CaHEM14 (encoding protoporphyrinogen oxidase) but not that of CaHEM15 (encoding ferrochelatase). There are thus profound differences between S. cerevisiae and C. albicans in terms of haem synthesis, cytochrome turnover and the role of frataxin in these processes. [source] The Angelic Doctor and the Stagirite: Thomas Aquinas and Contemporary ,Aristotelian' EthicsPROCEEDINGS OF THE ARISTOTELIAN SOCIETY (HARDBACK), Issue 1 2001M. W. F. Stone To what extent, if any, is the moral thought of Thomas Aquinas ,Aristotelian'? This question is not simply of historical interest, since it directs our attention to those areas of contemporary English-speaking moral philosophy where Thomas is discussed. In some quarters there is a tendency to classify Thomas as a thinker in the ,Aristotelian tradition', and his debt to Aristotle is thought to be apparent in his remarks on moral reasoning and virtue. Nowhere is this tendency more evident than in discussions of Thomas by supporters of modern virtue ethics. In this paper, I will argue that the relationship of Thomas's ethics to Aristotle is much more complicated than these discussions assume. Despite the strong and interesting affinities that exist between the practical philosophies of Thomas and Aristotle, the sum total of their common features can never disguise nor dilute the profound differences that separate them. The paper will conclude with some suggestions as to how an appreciation of these differences can enable us to cast Thomas's remarks on virtue in a different light. [source] Influence of temperature on corneas stored in culture medium.ACTA OPHTHALMOLOGICA, Issue 1 2003A comparative study using functional, morphological methods Abstract. Purpose:, To investigate the influence of storage temperature on corneal swelling and on endothelial morphology in cultured corneas. Material and methods:, Forty-eight rabbit corneas were separated into four groups of 12. The corneas were stored in culture medium at 37 ° (group 37), 34 ° (group 34), 31 ° (group 31) and 23 ° (room temperature) (group 23), respectively. All the corneas were monitored by weight recordings on days 0, 1, 2, 3, 4 and 7. On day 7, corneas were prepared for scanning electron microscopy and endothelial cell counts were performed. Results:, Lowering the temperature of the culture medium resulted in less swelling. Both temperature and storage time had significant effects on corneal swelling (p < 0.001). On day 7, the observed mean weight increase was 131.2%, 143.0%, 172.5% and 199.7% in groups 23, 31, 34 and 37, respectively. The estimated mean daily weight increase for the corneas were 2.6%, 4.0%, 9.1% and 16.0% in groups 23, 31, 34 and 37, respectively. Scanning electron microscopy showed an intact endothelial layer in all groups after 7 days and there were no statistically significant differences in endothelial counts between groups 23, 31 and 34. In group 37, the cell borders were difficult to distinguish after 7 days and no meaningful count could be performed. Conclusions:, The swelling rate of cultured corneas is significantly less at 23 ° and 31 ° than it is at 34 ° and 37 ° during the first week. This is most likely the result of a greatly increased barrier effect at lower temperatures. Whereas weight recording revealed profound differences between the groups, scanning electron microscopy and endothelial cell counting did not. The results support the hypothesis that storage at 37 ° is not optimal in culturing corneas. Lowering the temperature below body temperature, and even lower than 31 °, results in less corneal swelling. [source] | ||||||||||||||||