441 research outputs found
Heat transfer on a flat plate in helium at Mach numbers 67.3 and 87.6 and in hypersonic corner flow with air at Mach number of 19
Hypersonic heat transfer rates on flat plates in helium and in corner flow region with ai
Heat Transfer on a Flat Plate in Continuum to Rarefied Hypersonic Fows at Mach Numbers of 19.2 and 25.4
Surface heat transfer rates measured on flat plates in hypervelocity shock tunne
Black Holes as Effective Geometries
Gravitational entropy arises in string theory via coarse graining over an
underlying space of microstates. In this review we would like to address the
question of how the classical black hole geometry itself arises as an effective
or approximate description of a pure state, in a closed string theory, which
semiclassical observers are unable to distinguish from the "naive" geometry. In
cases with enough supersymmetry it has been possible to explicitly construct
these microstates in spacetime, and understand how coarse-graining of
non-singular, horizon-free objects can lead to an effective description as an
extremal black hole. We discuss how these results arise for examples in Type II
string theory on AdS_5 x S^5 and on AdS_3 x S^3 x T^4 that preserve 16 and 8
supercharges respectively. For such a picture of black holes as effective
geometries to extend to cases with finite horizon area the scale of quantum
effects in gravity would have to extend well beyond the vicinity of the
singularities in the effective theory. By studying examples in M-theory on
AdS_3 x S^2 x CY that preserve 4 supersymmetries we show how this can happen.Comment: Review based on lectures of JdB at CERN RTN Winter School and of VB
at PIMS Summer School. 68 pages. Added reference
CTCF binds to sites in the major histocompatibility complex that are rapidly reconfigured in response to interferon-gamma
Activation of the major histocompatibility complex (MHC) by interferon-gamma (IFN−γ) is a fundamental step in the adaptive immune response to pathogens. Here, we show that reorganization of chromatin loop domains in the MHC is evident within the first 30 min of IFN−γ treatment of fibroblasts, and that further dynamic alterations occur up to 6 h. These very rapid changes occur at genomic sites which are occupied by CTCF and are close to IFN−γ-inducible MHC genes. Early responses to IFN−γ are thus initiated independently of CIITA, the master regulator of MHC class II genes and prepare the MHC for subsequent induction of transcription
Anti-cancer effects and mechanism of actions of aspirin analogues in the treatment of glioma cancer
INTRODUCTION: In the past 25 years only modest advancements in glioma treatment have been made, with patient prognosis and median survival time following diagnosis only increasing from 3 to 7 months. A substantial body of clinical and preclinical evidence has suggested a role for aspirin in the treatment of cancer with multiple mechanisms of action proposed including COX 2 inhibition, down regulation of EGFR expression, and NF-κB signaling affecting Bcl-2 expression. However, with serious side effects such as stroke and gastrointestinal bleeding, aspirin analogues with improved potency and side effect profiles are being developed. METHOD: Effects on cell viability following 24 hr incubation of four aspirin derivatives (PN508, 517, 526 and 529) were compared to cisplatin, aspirin and di-aspirin in four glioma cell lines (U87 MG, SVG P12, GOS – 3, and 1321N1), using the PrestoBlue assay, establishing IC50 and examining the time course of drug effects. RESULTS: All compounds were found to decrease cell viability in a concentration and time dependant manner. Significantly, the analogue PN517 (IC50 2mM) showed approximately a twofold increase in potency when compared to aspirin (3.7mM) and cisplatin (4.3mM) in U87 cells, with similar increased potency in SVG P12 cells. Other analogues demonstrated similar potency to aspirin and cisplatin. CONCLUSION: These results support the further development and characterization of novel NSAID derivatives for the treatment of glioma
A bound on the entropy of supergravity?
We determine, in two independent ways, the number of BPS quantum states
arising from supergravity degrees of freedom in a system with fixed total D4D0
charge. First, we count states generated by quantizing the spacetime degrees of
freedom of 'entropyless' multicentered solutions consisting of anti-D0-branes
bound to a D6-anti-D6 pair. Second, we determine the number of free
supergravity excitations of the corresponding AdS_3 geometry with the same
total charge. We find that, although these two approaches yield a priori
different sets of states, the leading degeneracies in a large charge expansion
are equal to each other and that, furthermore, the number of such states is
parametrically smaller than that arising from the D4D0 black hole's entropy.
This strongly suggests that supergravity alone is not sufficient to capture all
degrees of freedom of large supersymmetric black holes. Comparing the free
supergravity calculation to that of the D6-anti-D6-D0 system we find that the
bound on the free spectrum imposed by the stringy exclusion principle (a
unitarity bound in the dual CFT) seems to be captured in the dynamics of the
fully interacting but classcial supergravity equations of motion.Comment: 33 pages, 5 figure
Comparison of the Ki-67 score and S-phase fraction as prognostic variables in soft-tissue sarcoma
Immunohistochemically determined Ki-67 scores and flow cytometrically determined S-phase fractions were successfully evaluated from the primary tumours of 123 patients with soft-tissue sarcoma. All patients had either limb or superficial trunk tumours. Ki-67 score correlated strongly with ploidy, S-phase fraction and grade. Ki-67 did not correlate with the size of the primary tumour. When analysed as a continuous variable, Ki-67 was a stronger predictor of both metastasis-free survival and disease-specific overall survival (P= 0.003 and 0.04 respectively) than was the S-phase fraction (P= 0.06 and 0.07 respectively). We tested the relevance of different cut-point values by dividing the whole material into two parts at every 10% (e.g. 10% of patients vs. the remaining 90%, 20% vs. 80%, etc.). We counted the relative risk and confidence interval at all these cut-off points. Ki-67 had good prognostic discriminating power irrespective of the cut-point value, but S-phase fraction lost its prognostic power at higher cut-point values. In conclusion, we found that Ki-67 is a useful prognostic tool in the treatment of soft-tissue sarcoma patients irrespective of the cut-point value. S-phase fraction can be used at lower cut-point values. © 1999 Cancer Research Campaig
Molecular and phenotypic characterisation of paediatric glioma cell lines as models for preclinical drug development.
Although paediatric high grade gliomas resemble their adult counterparts in many ways, there appear to be distinct clinical and biological differences. One important factor hampering the development of new targeted therapies is the relative lack of cell lines derived from childhood glioma patients, as it is unclear whether the well-established adult lines commonly used are representative of the underlying molecular genetics of childhood tumours. We have carried out a detailed molecular and phenotypic characterisation of a series of paediatric high grade glioma cell lines in comparison to routinely used adult lines
Widespread Expression of BORIS/CTCFL in Normal and Cancer Cells
BORIS (CTCFL) is the paralog of CTCF (CCCTC-binding factor; NM_006565), a ubiquitously expressed DNA-binding protein with diverse roles in gene expression and chromatin organisation. BORIS and CTCF have virtually identical zinc finger domains, yet display major differences in their respective C- and N-terminal regions. Unlike CTCF, BORIS expression has been reported only in the testis and certain malignancies, leading to its classification as a “cancer-testis” antigen. However, the expression pattern of BORIS is both a significant and unresolved question in the field of DNA binding proteins. Here, we identify BORIS in the cytoplasm and nucleus of a wide range of normal and cancer cells. We compare the localization of CTCF and BORIS in the nucleus and demonstrate enrichment of BORIS within the nucleolus, inside the nucleolin core structure and adjacent to fibrillarin in the dense fibrillar component. In contrast, CTCF is not enriched in the nucleolus. Live imaging of cells transiently transfected with GFP tagged BORIS confirmed the nucleolar accumulation of BORIS. While BORIS transcript levels are low compared to CTCF, its protein levels are readily detectable. These findings show that BORIS expression is more widespread than previously believed, and suggest a role for BORIS in nucleolar function
Deconstructing Insight: EEG Correlates of Insightful Problem Solving
Background:
Cognitive insight phenomenon lies at the core of numerous discoveries. Behavioral research indicates four salient features of insightful problem solving: (i) mental impasse, followed by (ii) restructuring of the problem representation, which leads to (iii) a deeper understanding of the problem, and finally culminates in (iv) an “Aha!” feeling of suddenness and obviousness of the solution. However, until now no efforts have been made to investigate the neural mechanisms of these constituent features of insight in a unified framework.
Methodology/Principal Findings:
In an electroencephalographic study using verbal remote associate problems, we identified neural correlates of these four features of insightful problem solving. Hints were provided for unsolved problems or after mental impasse. Subjective ratings of the restructuring process and the feeling of suddenness were obtained on trial-by-trial basis. A negative correlation was found between these two ratings indicating that sudden insightful solutions, where restructuring is a key feature, involve automatic, subconscious recombination of information. Electroencephalogram signals were analyzed in the space×time×frequency domain with a nonparametric cluster randomization test. First, we found strong gamma band responses at parieto-occipital regions which we interpreted as (i) an adjustment of selective attention (leading to a mental impasse or to a correct solution depending on the gamma band power level) and (ii) encoding and retrieval processes for the emergence of spontaneous new solutions. Secondly, we observed an increased upper alpha band response in right temporal regions (suggesting active suppression of weakly activated solution relevant information) for initially unsuccessful trials that after hint presentation led to a correct solution. Finally, for trials with high restructuring, decreased alpha power (suggesting greater cortical excitation) was observed in right prefrontal area.
Conclusions/Significance:
Our results provide a first account of cognitive insight by dissociating its constituent components and potential neural correlates
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