224 resultados para Lawrence, C. W.
Resumo:
We investigate the violation of Leggett's inequality for nonlocal realism using entangled coherent states and various types of local measurements. We prove mathematically the relation between the violation of the Clauser-Horne-Shimony-Holt form of Bell's inequality and Leggett's one when tested by the same resources. For Leggett inequalities, we generalize the nonlocal realistic bound to systems in Hilbert spaces larger than bidimensional ones and introduce an optimization technique that allows one to achieve larger degrees of violation by adjusting the local measurement settings. Our work describes the steps that should be performed to produce a self-consistent generalization of Leggett's original arguments to continuous-variable states.
Resumo:
The hypoxia-inducible factors (HIFs; isoforms HIF-1 alpha, HIF-2 alpha, HIF-3 alpha) mediate many responses to hypoxia. Their regulation is principally by oxygen-dependent degradation, which is initiated by hydroxylation of specific proline residues followed by binding of von Hippel-Lindau (VHL) protein. Chuvash polycythemia is a disorder with elevated HIF. It arises through germline homozygosity for hypomorphic VHL alleles and has a phenotype of hematological, cardiopulmonary, and metabolic abnormalities. This study explores the phenotype of two other HIF pathway diseases: classic VHL disease and HIF-2 alpha gain-of-function mutation. No cardiopulmonary abnormalities were detected in classic VHL disease. HIF-2 alpha gain-of-function mutations were associated with pulmonary hypertension, increased cardiac output, increased heart rate, and increased pulmonary ventilation relative to metabolism. Comparison of the HIF-2 alpha gain-of-function responses with data from studies of Chuvash polycythemia suggested that other aspects of the Chuvash phenotype were diminished or absent. In classic VHL disease, patients are germline heterozygous for mutations in VHL, and the present results suggest that a single wild-type allele for VHL is sufficient to maintain normal cardiopulmonary function. The HIF-2 alpha gain-of-function phenotype may be more limited than the Chuvash phenotype either because HIF-1 alpha is not elevated in the former condition, or because other HIF-independent functions of VHL are perturbed in Chuvash polycythemia.-Formenti, F., Beer, P. A., Croft, Q. P. P., Dorrington, K. L., Gale, D. P., Lappin, T. R. J., Lucas, G. S., Maher, E. R., Maxwell, P. H., McMullin, M. F., O'Connor, D. F., Percy, M. J., Pugh, C. W., Ratcliffe, P. J., Smith, T. G., Talbot, N. P., Robbins, P. A. Cardiopulmonary function in two human disorders of the hypoxia-inducible factor (HIF) pathway: von Hippel-Lindau disease and HIF-2 alpha gain-of-function mutation. FASEB J. 25, 2001-2011 (2011). www.fasebj.org
Resumo:
We present photometric and spectroscopic observations of a luminous Type IIP Supernova (SN) 2009kf discovered by the Pan-STARRS 1 (PS1) survey and also detected by the Galaxy Evolution Explorer. The SN shows a plateau in its optical and bolometric light curves, lasting approximately 70 days in the rest frame, with an absolute magnitude of M-V = - 18.4 mag. The P-Cygni profiles of hydrogen indicate expansion velocities of 9000 km s(-1) at 61 days after discovery which is extremely high for a Type IIP SN. SN 2009kf is also remarkably bright in the near-ultraviolet (NUV) and shows a slow evolution 10-20 days after optical discovery. The NUV and optical luminosity at these epochs can be modeled with a blackbody with a hot effective temperature (T similar to 16,000 K) and a large radius (R similar to 1 x 10(15) cm). The bright bolometric and NUV luminosity, the light curve peak and plateau duration, the high velocities, and temperatures suggest that 2009kf is a Type IIP SN powered by a larger than normal explosion energy. Recently discovered high-z SNe (0.7
Resumo:
This article is concerned with understanding the behavior of polyethylene terephthalate (PET) in the injection stretch blow molding (ISBM) process where it is typically biaxially stretched to form bottles for the packaging industry. A comprehensive experimental study was undertaken, analyzing the behavior of three different grades of PET under constant width (CW), simultaneous (EB), and sequential (SQ) equal biaxial deformation. Experiments were carried out at temperature and strain rate ranges of 80–110C and 1 /s to 32 /s, respectively, to different stretch ratios. Results show that the biaxial deformation behavior of PET exhibits a strong dependency on forming temperature, strain rate, stretch ratio,deformation mode, and molecular weight. The tests were also monitored via a high speed thermal image camera which showed an increase in temperature between 5C and 15C observed depending on the stretch conditions.
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Immersed shannies (Blennius pholis) showed peak locomotory activity coincident with daylight high tides. Emersion caused cessation of breathing and bradycardia though Q02 was little affected. Q02 fell, however, when the abdomen was enclosed in an impermeable sheath to block cutaneous respiration. Gulping of air into the extensively vascular oesophagus probably also acts as a means of aerial respiration. Reimmersion of fish caused a transient bradycardia followed by a tachycardia and a fall in Q02 followed subsequently by a rise. The results are discussed in relation to the behavioural, circulatory, respiratory and morphological adaptations of the shanny to the intertidal habitat.
Resumo:
Tissue microarray (TMA) is a high throughput analysis tool to identify new diagnostic and prognostic markers in human cancers. However, standard automated method in tumour detection on both routine histochemical and immunohistochemistry (IHC) images is under developed. This paper presents a robust automated tumour cell segmentation model which can be applied to both routine histochemical tissue slides and IHC slides and deal with finer pixel-based segmentation in comparison with blob or area based segmentation by existing approaches. The presented technique greatly improves the process of TMA construction and plays an important role in automated IHC quantification in biomarker analysis where excluding stroma areas is critical. With the finest pixel-based evaluation (instead of area-based or object-based), the experimental results show that the proposed method is able to achieve 80% accuracy and 78% accuracy in two different types of pathological virtual slides, i.e., routine histochemical H&E and IHC images, respectively. The presented technique greatly reduces labor-intensive workloads for pathologists and highly speeds up the process of TMA construction and provides a possibility for fully automated IHC quantification.
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Hypoxia results in adaptive changes in the transcription of a range of genes including erythropoietin. An important mediator is hypoxia-inducible factor-1 (HIF-1), a DNA binding complex shown to contain at least two basic helix-loop-helix PAS-domain (bHLH-PAS) proteins, HIF-1 alpha and aryl hydrocarbon nuclear receptor translocator (ARNT), In response to hypoxia, HIF-1 alpha is activated and accumulates rapidly in the cell. Endothelial PAS domain protein 1 (EPAS-1) is a recently identified bHLH-PAS protein with 48% identity to HIF-1 alpha, raising the question of its role in responses to hypoxia. We developed specific antibodies and studied expression and regulation of EPAS-1 mRNA and protein across a range of human cell lines. EPAS-1 was widely expressed, and strongly induced by hypoxia at the level of protein but not mRNA. Comparison of the effect of a range of activating and inhibitory stimuli showed striking similarities in the EPAS-1 and HIF-1 alpha responses. Although major differences were observed in the abundance of EPAS-1 and HIF-1 alpha in different cell types, differences in the inducible response were subtle with EPAS-1 protein being slightly more evident in normoxic and mildly hypoxic cells. Functional studies in a mutant cell line (Ka13) expressing neither HIF-1 alpha nor EPAS-1 confirmed that both proteins interact with hypoxically responsive targets, but suggest target specificity with greater EPAS-1 transactivation (relative to HIF-1 alpha transactivation) of the VEGF promoter than the LDH-A promoter. (C) 1998 by The American Society of Hematology.
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Transient receptor potential canonical (TRPC) channels are Ca(2+)-permeable nonselective cation channels implicated in diverse physiological functions, including smooth muscle contractility and synaptic transmission. However, lack of potent selective pharmacological inhibitors for TRPC channels has limited delineation of the roles of these channels in physiological systems. Here we report the identification and characterization of ML204 as a novel, potent, and selective TRPC4 channel inhibitor. A high throughput fluorescent screen of 305,000 compounds of the Molecular Libraries Small Molecule Repository was performed for inhibitors that blocked intracellular Ca(2+) rise in response to stimulation of mouse TRPC4ß by µ-opioid receptors. ML204 inhibited TRPC4ß-mediated intracellular Ca(2+) rise with an IC(50) value of 0.96 µm and exhibited 19-fold selectivity against muscarinic receptor-coupled TRPC6 channel activation. In whole-cell patch clamp recordings, ML204 blocked TRPC4ß currents activated through either µ-opioid receptor stimulation or intracellular dialysis of guanosine 5'-3-O-(thio)triphosphate (GTP?S), suggesting a direct interaction of ML204 with TRPC4 channels rather than any interference with the signal transduction pathways. Selectivity studies showed no appreciable block by 10-20 µm ML204 of TRPV1, TRPV3, TRPA1, and TRPM8, as well as KCNQ2 and native voltage-gated sodium, potassium, and calcium channels in mouse dorsal root ganglion neurons. In isolated guinea pig ileal myocytes, ML204 blocked muscarinic cation currents activated by bath application of carbachol or intracellular infusion of GTP?S, demonstrating its effectiveness on native TRPC4 currents. Therefore, ML204 represents an excellent novel tool for investigation of TRPC4 channel function and may facilitate the development of therapeutics targeted to TRPC4.
Resumo:
We present the discovery of two ultraluminous supernovae (SNe) at z approximate to 0.9 with the Pan-STARRS1 Medium Deep Survey. These SNe, PS1-10ky and PS1-10awh, are among the most luminous SNe ever discovered, comparable to the unusual transients SN 2005ap and SCP 06F6. Like SN 2005ap and SCP 06F6, they show characteristic high luminosities (M-bol approximate to -22.5 mag), blue spectra with a few broad absorption lines, and no evidence for H or He. We have constructed a full multi-color light curve sensitive to the peak of the spectral energy distribution in the rest-frame ultraviolet, and we have obtained time series spectroscopy for these SNe. Given the similarities between the SNe, we combine their light curves to estimate a total radiated energy over the course of explosion of (0.9-1.4) x 10(51) erg. We find photospheric velocities of 12,000-19,000 km s(-1) with no evidence for deceleration measured across similar to 3 rest-frame weeks around light curve peak, consistent with the expansion of an optically thick massive shell of material. We show that, consistent with findings for other ultraluminous SNe in this class, radioactive decay is not sufficient to power PS1-10ky, and we discuss two plausible origins for these events: the initial spin-down of a newborn magnetar in a core-collapse SN, or SN shock breakout from the dense circumstellar wind surrounding a Wolf-Rayet star.
Resumo:
SN 2009ku, discovered by Pan-STARRS-1, is a Type Ia supernova (SN Ia), and a member of the distinct SN 2002cx-like class of SNe Ia. Its light curves are similar to the prototypical SN 2002cx, but are slightly broader and have a later rise to maximum in g. SN 2009ku is brighter (similar to 0.6 mag) than other SN 2002cx-like objects, peaking at M-V = -18.4 mag, which is still significantly fainter than typical SNe Ia. SN 2009ku, which had an ejecta velocity of similar to 2000 km s(-1) at 18 days after maximum brightness, is spectroscopically most similar to SN 2008ha, which also had extremely low-velocity ejecta. However, SN 2008ha had an exceedingly low luminosity, peaking at M-V = -14.2 mag, similar to 4 mag fainter than SN 2009ku. The contrast of high luminosity and low ejecta velocity for SN 2009ku is contrary to an emerging trend seen for the SN 2002cx class. SN 2009ku is a counterexample of a previously held belief that the class was more homogeneous than typical SNe Ia, indicating that the class has a diverse progenitor population and/or complicated explosion physics. As the first example of a member of this class of objects from the new generation of transient surveys, SN 2009ku is an indication of the potential for these surveys to find rare and interesting objects.