5,332 research outputs found

    The role of the retinoblastoma protein (Rb) in the nuclear localization of BAG-1: implications for colorectal tumour cell survival

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    Although the retinoblastoma susceptibility gene RB1 is inactivated in a wide variety of human cancers, the retinoblastoma protein (Rb) has been shown to be overexpressed in colon cancers, which is linked to the anti-apoptotic function of the protein. However, the mechanisms by which Rb regulates apoptosis are yet to be fully elucidated. We have established that Rb interacts with the anti-apoptotic BAG-1 (Bcl-2 associated athanogene-1) protein, and that a decrease in nuclear localization of BAG-1 is detectable when the interaction between Rb and BAG-1 is disrupted by expression of the E7 viral oncoprotein. Interestingly, although reported as deregulated in colorectal cancers, we have found that BAG-1 expression is also altered in small adenomas, where its localization was found to be predominantly nuclear. In addition, we have established that maintenance of high nuclear BAG-1 in vitro increases the resistance of adenoma-derived cells to g-radiation-induced apoptosis. Our work suggests a novel function for Rb, involving modulation of the subcellular localization of BAG-1. We have found predominant nuclear BAG-1 localization in small adenomas, and suggest that BAG-1 may promote colorectal tumour cell survival by making colonic epithelial cells less sensitive to DNA damage.<br/

    Feshbach spectroscopy of an ultracold Rb-Cs mixture

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    This thesis reports the observation of interspecies Feshbach resonances in an ultracold mixture of Rb and Cs atoms. A versatile combined magnetic and optical potential has been designed and constructed which is capable of bringing both 87Rb^{87}\rm{Rb} and 133Cs^{133}\rm{Cs} to degeneracy, and reaching high phase-space density in 85Rb^{85}\rm{Rb}. High phase-space density mixtures are the first step required in the production of ultracold polar molecules, the topic of much current research. The apparatus capitalises on the efficient capture of atoms by a magnetic trap from a magneto-optical trap, and the efficient sympathetic cooling of Cs by Rb therein. Upon transfer to the crossed optical dipole trap condensates in excess of 1×1061\times10^{6} 87Rb^{87}\rm{Rb} atoms and approximately 1×1051\times10^{5} 133Cs^{133}\rm{Cs} atoms are produced after direct evaporation and gravito-magnetic tilting of the potential. The observation of six interspecies 87Rb^{87}\rm{Rb}-133Cs^{133}\rm{Cs} Feshbach resonances are reported, three of which had only been predicted theoretically, allowing testing and development of the theoretical model. Furthermore, the extrapolation of this model has predicted numerous Feshbach resonances between 85Rb^{85}\rm{Rb} and 133Cs^{133}\rm{Cs}, none of which have been experimentally observed prior to this work. The versatile nature of this apparatus is discussed, including the application of the current system to cooling of 85Rb^{85}\rm{Rb}. Initial experiments observed seven interspecies resonances, including a broad s-wave resonance at a magnetic field of (644±2)(644\pm2) G which is in excellent agreement with the theoretical prediction. Further work has revealed that fourteen Feshbach resonances exist in the 0-700 G magnetic field range between 85Rb^{85}\rm{Rb} and 133Cs^{133}\rm{Cs} atoms in the 2,+2\left|2,+2\right\rangle and 3,+3\left|3,+3\right\rangle states, respectively. Several of these resonances would be ideal for magneto-association of RbCs molecules, prior to transfer to the rovibrational ground-state

    The retinoblastoma protein (Rb) as an anti-apoptotic factor: expression of Rb is required for the anti-apoptotic function of BAG-1 protein in colorectal tumour cells

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    Although the retinoblastoma-susceptibility gene RB1 is inactivated in a wide range of human tumours, in colorectal cancer, the retinoblastoma protein (Rb) function is often preserved and the RB locus even amplified. Importantly, we have previously shown that Rb interacts with the anti-apoptotic Bcl-2 associated athanogene 1 (BAG-1) protein, which is highly expressed in colorectal carcinogenesis. Here we show for the first time that Rb expression is critical for BAG-1 anti-apoptotic activity in colorectal tumour cells. We demonstrate that Rb expression not only increases the nuclear localisation of the anti-apoptotic BAG-1 protein, but that expression of Rb is required for inhibition of apoptosis by BAG-1 both in a c-irradiated Saos-2 osteosarcoma cell line and colorectal adenoma and carcinoma cell lines. Further, consistent with the fact that nuclear BAG-1 has previously been shown to promote cell survival through increasing nuclear factor (NF)-jB activity, we demonstrate that the ability of BAG-1 to promote NF-jB activity is significantly inhibited by repression of Rb expression. Taken together, data presented suggest a novel function for the Rb, promoting cell survival through regulating the function of BAG-1. As BAG-1 is highly expressed in the majority of colorectal tumours, targeting the Rb–BAG-1 complex to promote apoptosis has exciting potential for future therapeutic development

    A Quantum Degenerate Mixture of 87^{87}Rb and 133^{133}Cs

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    This thesis reports the formation of a dual-species Bose-Einstein condensate of 87^{87}Rb and 133^{133}Cs in the same trapping potential. Quantum degenerate mixtures exhibit rich physics inaccessible to single species experiments and provide an ideal starting point for the creation of ultracold dipolar molecules. These molecules offer a wealth of new research avenues including precision metrology, quantum simulation and computation. The experimental method exploits the efficient sympathetic cooling of 133^{133}Cs via elastic collisions with 87^{87}Rb, initially in a magnetic quadrupole trap and subsequently in a levitated optical trap. Evaporative cooling in the dipole trap must compete against a high interspecies three-body inelastic collision rate \mbox{10251026\sim10^{-25}-10^{-26}~cm6/^{6}/s}. The two condensates each contain up to \mbox{2×1042\times10^{4}} atoms and exhibit a striking phase separation, revealing the mixture to be immiscible due to strong repulsive interspecies interactions. Sacrificing all the 87^{87}Rb during the cooling leads to the creation of single-species 133^{133}Cs condensates of up to \mbox{6×1046\times10^{4}} atoms. In addition this thesis reports the observation of an interspecies Feshbach resonance at 181.7(5)~G and the creation of a pure sample of Cs2_{2} molecules via magneto-association on the 4(g)4 resonance at 19.8~G. These results represent important steps towards the creation of ultracold polar RbCs molecules

    Tween girls’ perception of gender roles and gender identities: a qualitative study

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    PurposeThe present study aims to examine girls' perception of gender roles and gender identities in Hong Kong.Design/methodology/approachA total of 16 girls aged 10 to 12 were asked to take pictures from the media that could illustrate “what girls or women should or should not be; and what girls or women should or should not do”. Qualitative interviews were conducted.FindingsAnalysis of interviews and images captured found that tween girls' perceived gender roles for females were based on a mixture of traditional and contemporary role models. Girls in Hong Kong demonstrated conservatism in sexuality. Sexy outlook and pre‐marital sexual relations were considered inappropriate. Tween girls showed concern about global as well as domestic social agendas. They used a variety of media and showed interest in contents primarily for adults.Research limitations/implicationsThe study was based on a convenience sample. The interviewees came from middle to lower income families, limiting the validity for generalization. Further quantitative study is needed to establish benchmarks.Practical implicationsThis study will help in understanding the kinds of media images that attract the attention of female tweens and what those images mean to them. The study can serve as a guideline for marketing communication aimed at this target group, particularly for skincare, beauty, and cosmetic marketers.Originality/valueThe first novel idea that is being used in this research is the combination of visual method and the application of qualitative methodology to the study of media effects. The second novel idea is the use of interviewees as data‐collectors. The methodology enables contextually relevant questions and to understand the meaning of the images captured.</jats:sec

    TAP deficiency syndrome: chronic rhinosinusitis and conductive hearing loss

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    Nose-ear-throat manifestations of immunodeficiency disorders represent a diagnostic challenge for clinicians as these diseases often constitute the initial sign for connective disorders or autoimmune disease. The history of chronic rhinosinusitis and conductive hearing loss is often non specific. Therefore attention to an HLA class I deficiency must be considered if the disease has not been diagnosed on routine examination. One of the syndromes is due to a defective TAP complex, the peptide transporter complex associated with antigen presentation. Herein, we report two sisters with TAP-deficiency. The treatment of choice for TAP-deficient patients is conservative

    Realisation of a cold mixture of rubidium and caesium

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    This thesis describes a new apparatus designed to study cold, ultracold, and quantum degenerate mixtures of rubidium and caesium atoms. The Rb- Cs mixture is prepared using a double magneto-optical trap (MOT) system in which a two-species pyramid MOT acts as a source of cold atoms for a 'science' MOT. The first results of experiments on the magneto-optically trapped mixture are presented, including measurements of trap loss rates due to single-species and interspecies inelastic collisions. A technique for reducing interspecies loss by spatially separating the MOTs during loading is described. This technique allows 50-50 mixtures of Rb and Cs atoms to be loaded into a magnetic trap at close to their respective maximum single- species atom numbers. Alternatively, one species can be loaded with arbitrarily small amounts of the other. The displaced MOT technique is thus аn excellent starting point for investigations of interspecies Feshbach resonances and sympathetic cooling of Rb-Cs mixtures in magnetic and optical traps. In addition, a model of polarisation spectroscopy based on numerical integration of population rate equations is described. Theoretical polarisation spectra generated by the model are shown to agree with experimental spectra for the F = I + 1/2 → F' transitions in Rb and Cs. An investigation of the sub-Doppler dichroic atomic vapour laser locking (DAVLL) technique demonstrates how locking signals can be optimised for the Rb D2 transitions. The role of polarisation purity in generating the spectra is discussed, and impurities are modeled using a Jones matrix approach. Comparisons with polarisation spectroscopy and DAVLL are used to enhance understanding of atom-light interactions in spectroscopic systems, and indicate methods for optimising locking signals for use in cold atom experiments

    Liquid structure of Rb-Hg alloys studied by neutron diffraction

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    The structures of liquid Rb–Hg alloys were studied as a function of composition by neutron diffraction. In the intermediate Rb concentration range, the obtained structure factors show a small prepeak, which may be an evidence of the formation of Hg polyanion units in liquids. The Reverse Monte Carlo (RMC) analysis was applied to separate the total radial distribution function into the corresponding partial radial distribution functions. Up to 10 at.% Rb, no obvious changes are found for the first peak position of the partial radial distribution functions of the Hg–Hg pair and that of the Hg–Rb pair. The first peak position between the Hg–Rb pairs increases above 20 at.% Rb. In addition to the first peak, a subpeak between Hg–Hg pairs can be seen in the large distance. At 60 at.% Rb, the nearest neighbor distance between Hg atoms shows the closest value in the concentration range studied. These results indicate that with the progress of charge transfer the solvation structure in the dilute Rb concentration range changes into the structure containing polyanions composed of Hg species

    Increased statin prescribing in patients with diabetes after the introduction of the NSF for Coronary Heart Disease

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    Cardiovascular disease accounts for 70% of deaths in people with diabetes. This is partly due to their abnormal lipoprotein profiles. Several studies have shown that the prescription of statins to this group of people can greatly reduce the risk of death. The National Service Framework for Coronary Heart Disease (NSF for CHD), introduced in March 2000, set targets for treating people at high risk of death from CHD. Our study looked at 14 practices in Surrey to see whether the NSF has had an impact on statin prescribing in people with diabetes over the age of 40. There has been a 21% increase in the prevalence of diabetes between 1999 and 2002. We have also shown a 74% increase in the prescribing of statins to people with diabetes following the introduction of the NSF for CHD. The increase in the number of people receiving statins has cost implications for primary care trusts

    Fractional Edge Cover Number of Model RB

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    Model RB is a random constraint satisfaction problem with a growing domain size, which exhibits exact phase transition phenomena. Many hard instances with planted solutions can be generated via Model RB, to be used as benchmarks for algorithmic competitions and researches. In the past, some structural parameters of constraint hypergraphs are analyzed to show hardness of Model RB, such as hinge width, decycling number, treewidth, and hypertree width. In this paper, one more structural parameter of constraint hypergraphs of Model RB, namely the fractional edge cover number, is analyzed. We show upper and lower bounds on the fractional edge cover number of Model RB. In particular, the fractional edge cover number of Model RB is shown to be asymptotically linear in the number of variables, like hinge width, decycling number, treewidth and hypertree width. These results together provide further evidences on the hardness of Model RB.EICPCI-S(ISTP)[email protected]
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